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Full text of "Management of Cancer Pain, Clinical Practice Guideline Number 9"

Clinical Practice Guideline 



Number 9 

Management of 
Cancer Pain 



'0 
Won) 



'0013-733; 



U.S. Department of Health and Human Services 

Public Health Service 

Agency for Health Care Policy and Research 



The Agency for Health Care Policy and Research (AHCPR) was 
established in December 1989 under Public Law 101-239 (Omnibus 
Budget Reconciliation Act of 1989) to enhance the quality, appropri- 
ateness, and effectiveness of health care services and access to these 
services. AHCPR carries out its mission by conducting and supporting 
general health services research, including medical effectiveness 
research, facilitating development of clinical practice guidelines, and 
disseminating research findings and guidelines to health care 
providers, policymakers, and the public. 

The legislation also established within AHCPR the Office of the 
Forum for Quality and Effectiveness in Health Care (the Forum). The 
Forum has primary responsibility for facilitating the development, 
periodic review, and updating of clinical practice guidelines. The 
guidelines will assist practitioners in the prevention, diagnosis, treat- 
ment, and management of clinical conditions. 

Other components of AHCPR include the following. The Center 
for Medical Effectiveness Research has principal responsibility for 
patient outcomes research and studies of variations in clinical practice. 
The Center for General Health Services Extramural Research 
supports research on primary care, the cost and financing of health 
care, and access to care for underserved and rural populations. The 
Center for General Health Services Intramural Research uses large 
data sets for policy research on national health care expenditures and 
utilization, hospital studies, and long-term care. The Center for 
Research Dissemination and Liaison produces and disseminates find- 
ings from AHCPR-supported research, including guidelines, and 
conducts research on dissemination methods. The Office of Health 
Technology Assessment responds to requests from Federal health 
programs for assessment of health care technologies. The Office of 
Science and Data Development develops specialized data bases for 
patient outcomes research. 

Guidelines are available in formats suitable for health care practi- 
tioners, the scientific community, educators, and consumers. AHCPR 
invites comments and suggestions from users for consideration in 
development and updating of future guidelines. Please send written 
comments to Director, Office of the Forum, AHCPR, Willco Building, 
Suite 310, 6000 Executive Boulevard, Rockville, MD 20852. 



Clinical Practice Guideline 
Number 9 



Management of 
Cancer Pain 



Management of Cancer Pain 
Guideline Panel 

Ada Jacox, RN, PhD (Co-Chair) 
Daniel B. Carr, MD (Co-Chair) 
Richard Payne, MD (Co-Chair) 
Charles B. Berde, MD, PhD 
William Brietbart, MD 
Joanna M. Cain, MD 
C. Richard Chapman, PhD 
Charles S. Cleeland, PhD 
Betty R. Ferrell, RN, PhD 
Rebecca S. Finley, PharmD, MS 
Nancy O. Hester, RN, PhD 
C. Stratton Hill, Jr., MD 
W. David Leak, MD 
Arthur G. Lipman, PharmD 
Catherine L. Logan 
Charles L. McGarvey, PT, MS 
Christine A. Miaskowski, RN, PhD 
David Stevenson Mulder, MD 
Judith A. Paice, RN, PhD 
Barbara S. Shapiro, MD 
Edward B. Silberstein, MD 
Rev. Robert S. Smith, PhD 
Jeanne Stover 
Carole V. Tsou, MD 
Loretta Vecchiarelli 
David E. Weissman, MD 

U.S. Department of Health and Human Services 

Public Health Service 

Agency for Health Care Policy and Research 

AHCPR Publication No. 94-0592 
March 1994 



Guideline Development and Use 

Guidelines are systematically developed statements to assist practi- 
tioner and patient decisions about appropriate health care for specific 
clinical conditions. This guideline was developed by a multidisciplin- 
ary panel of private-sector clinicians and other experts convened by 
the Agency for Health Care Policy and Research (AHCPR). The 
panel employed an explicit, science-based methodology and expert 
clinical judgment to develop specific statements on patient assessment 
and management for the clinical condition selected. 

Extensive literature searches were conducted, and critical reviews 
and syntheses were used to evaluate empirical evidence and signifi- 
cant outcomes. Peer review and field review were undertaken to eval- 
uate the validity, reliability, and utility of the guideline in clinical prac- 
tice. The panel's recommendations are primarily based on the 
published scientific literature. When the scientific literature was 
incomplete or inconsistent in a particular area, the recommendations 
reflect the professional judgment of panel members and consultants. 
In some instances, there was not unanimity of opinion. 

The guideline reflects the state of knowledge, current at the time of 
publication, on effective and appropriate care. Given the inevitable 
changes in the state of scientific information and technology, periodic 
review, updating, and revision will be done. We believe that the 
AHCPR-assisted clinical guideline development process will make 
positive contributions to the quality of care in the United States. We 
encourage practitioners and patients to use the information provided 
in this clinical practice guideline. The recommendations may not be 
appropriate for use in all circumstances. Decisions to adopt any partic- 
ular recommendation must be made by the practitioner in light of 
available resources and circumstances presented by individual patients. 

J. Jarrett Clinton, MD 
Administrator 

Agency for Health Care Policy and Research 



Publication of this guideline does not necessarily represent endorsement by the 
U.S. Department of Health and Human Services. 



Foreword 

Cancer is increasingly prevalent in the United States, and the pain 
associated with it is frequently undertreated. Cancer is diagnosed in 
over one million Americans annually, and one of five deaths in the 
United States — about 1,400 per day — results from cancer. 

Patients with cancer often have multiple pain problems, but in 
most patients, the pain can be effectively controlled. Nevertheless, 
undertreatment is common because of a lack of knowledge by clini- 
cians about effective assessment and management, negative attitudes 
of patients and clinicians toward the use of drugs for pain relief, and a 
variety of problems related to drug regulations, and the cost of and 
reimbursement for effective pain management. 

This guideline was developed by an interdisciplinary panel of clini- 
cians, patients, researchers, and experts in health policy. The guideline 
provides a synthesis of scientific research and expert judgment to make 
recommendations on pain assessment and management. Approximately 
470 health care professionals and 70 patients were involved either as 
consultants and peer reviewers or as participants in pilot testing. 

The Clinical Practice Guideline for the Management of Cancer 
Pain was commissioned by the Agency for Health Care Policy and 
Research (AHCPR). It follows and makes reference to an earlier 
guideline on acute pain management after surgery or trauma, also 
commissioned by AHCPR. The cancer pain guideline includes a 
section on the management of HIV positive/AIDS-related pain 
because of similarities in the sources of pain and the management 
approaches. This guideline is designed to help clinicians understand 
the assessment and treatment of cancer pain and associated symp- 
toms. It reflects a multimodal approach to the management of pain, 
and it emphasizes the need for careful and continuous assessment to 
match interventions to the sources of pain in individual patients. 



in 



Abstract 

Cancer is diagnosed in over one million Americans annually, and 
one of five deaths in the United States — about 1,400 per day — result 
from cancer. Despite recent advances in the understanding of pain and 
pain management approaches, pain control remains a significant prob- 
lem for patients with cancer. This guideline is designed to help any 
clinician who works with any oncology patient in any setting to under- 
stand the assessment and treatment of pain and associated symptoms. 

The guideline was developed by an interdisciplinary panel of clini- 
cians, patients, and experts in health policy. The panel used a combi- 
nation of scientific evidence and expert judgment to make recommen- 
dations about pain management in patients with cancer. 

The guideline makes recommendations about the assessment and 
management of pain. Interventions described include the use of 
(1) analgesics and adjuvant drugs; (2) cognitive/behavior strategies; 
(3) physical modalities; (4) palliative radiation and antineoplastic 
therapies; (5) nerve blocks; and (6) palliative and ablative surgery. 

The cost of cancer pain in suffering, disability, and quality of life is 
high. The guidelines recommend that cancer pain be treated aggres- 
sively by pharmacologic and nonpharmacologic approaches. In most 
instances, pain can be treated effectively with relatively low-cost, 
noninvasive therapies. Given this evidence, health system barriers that 
interfere with effective pain management — such as restrictive legisla- 
tion regarding the uses of opioid analgesics and third-party payer 
practices that do not reimburse for less invasive interventions — should 
be changed. 

This document is in the public domain and may be used and reprinted 
without special permission, except for those copyrighted materials noted 
for which further reproduction is prohibited without the specific permis- 
sion of copyright holders. AHCPR appreciates citation as to source, and 
the suggested format is provided below: 

Jacox A, Carr DB, Payne R, et al. Management of Cancer Pain. Clinical 
Practice Guideline No. 9. AHCPR Publication No. 94-0592. Rockville, 
MD. Agency for Health Care Policy and Research, U.S. Department of 
Health and Human Services, Public Health Service, March 1994. 



Dedication 

The Clinical Practice Guideline for the Management of Cancer 
Pain is dedicated to the memory of Jeanne Stover, a member of the 
panel that developed the guidelines. Jeanne represented the National 
Coalition for Cancer Survivorship on the panel. A 23-year survivor of 
breast cancer, she had metastatic disease during the last 9 years of her 
life and succumbed to this disease during her tenure as a panel 
member. She was a founding member of Living Through Cancer, a 
cancer self-help group in Albuquerque, New Mexico. The panel 
appreciates the insights and wisdom that Jeanne shared with us. 



VI 



Panel Members 

Ada Jacox, RN, PhD, FAAN, (1991-94) 
Co-Chair 

Independence Foundation Chair in Health Policy 

School of Nursing 

The Johns Hopkins University 

Baltimore, Maryland 

Specialties: Health Policy, Outcomes Research 

Daniel B. Carr, MD, Co-Chair, (1991-92) 

Special Consultant (1992-94) 
Director, Division of Pain Management 
Department of Anesthesia 
Massachusetts General Hospital 
Boston, Massachusetts 
Specialties: Anesthesiology, Endocrinology 

Richard Payne, MD, Member (1991-94) 

Co-Chair (1992-94) 

Director, Pain and Symptom Management Section 

MD Anderson Cancer Center 

Houston, Texas 

Specialties: Neurology, Oncology 

Charles B. Berde, MD, PhD (1992-94) 

Director, Pain Treatment Service 

Children's Hospital 

Boston, Massachusetts 

Specialties: Pediatrics, Anesthesia, Critical Care 

William Breitbart, MD (1991-94) 

Associate Member 

Memorial Sloan-Kettering Cancer Center 

New York, New York 

Specialty: Psychiatry, Internal Medicine 

Joanna M. Cain, MD (1992-94) 

Director, Women's Clinic 

Division of Gynecologic Oncology 

University of Washington Hospital 

Seattle, Washington 

Specialties: Obstetrics, Gynecologic Oncology 



vn 



C. Richard Chapman, PhD (1991-92) 

Professor, Department of Anesthesiology 
University of Washington School of Medicine 
Director, Pain and Toxicity Research Program 
Fred Hutchinson Cancer Research Center 
Seattle, Washington 
Specialty: Psychology 

Charles S. Cleeland, PhD (1992-94) 

Director, Pain Research Group 

Professor, Neurology 

Department of Neurology 

University of Wisconsin Medical School 

Madison, Wisconsin 

Specialty: Psychology 

Betty R. Ferrell, RN, PhD, FAAN (1991-94) 

Associate Research Scientist, Nursing Research 
City of Hope Medical Center 
Duarte, California 
Specialties: Oncology, Nursing 

Rebecca S. Finley, PharmD, MS (1992-94) 

Head, Section of Pharmacy Services 
University of Maryland Cancer Center 
Associate Professor of Oncology 
Associate Professor of Pharmacy Practice 
University of Maryland School of Pharmacy 
Baltimore, Maryland 
Specialty: Institutional Pharmacy 

Nancy O. Hester, RN, PhD, FAAN (1991-94) 

Associate Professor, School of Nursing 
University of Colorado Health Sciences Center 
Denver, Colorado 
Specialties: Pediatrics, Research Methods 

C. Stratton Hill, Jr., MD (1991-92) 

Professor of Medicine 

University of Texas 

MD Anderson Cancer Center 

Houston, Texas 

Specialty: Oncology 



vm 



W. David Leak, MD, FACPM (1992-94) 

Medical Director, Pain Control Consultants 
Adjunct Staff, Cleveland Clinic Foundation 
Westerville, Ohio 
Specialty: Pain Medicine 

Arthur G. Lipman, PharmD (1991-92) 

Professor of Clinical Pharmacy 

College of Pharmacy 

University of Utah 

Salt Lake City, Utah 

Specialty: Pharmacology in Pain Symptom Control 

Catherine L. Logan (1992-94) 

Executive Director and Founder, Living Through Cancer, Inc. 
Board of Advisors, National Coalition for Cancer Survivorship 
Albuquerque, New Mexico 
Consumer Representative 

Charles L. McGarvey, PT, MS (1991-92) 

Chief, Physical Therapy Section 
Rehabilitation Medicine Department 
Warren G. Magnuson Clinical Center 
National Institutes of Health 
Bethesda, Maryland 
Specialty: Physical Therapy 

Christine A. Miaskowski, RN, PhD, FAAN (1991-92) 

Associate Professor, Department of Physiological Nursing 
University of California, San Francisco 
San Francisco, California 
Specialty: Oncology 

David Stevenson Mulder, MD (1991-92) 

Professor of Surgery, McGill University 
Surgeon-in-Chief, Montreal General Hospital 
Montreal, Quebec, Canada 
Specialty: Cardiothoracic Surgery 

Judith A. Paice, RN, PhD (1992-94) 

Clinical Specialist, Pain Management 
Neuroscience Institute 

Rush-Presbyterian-St. Luke's Medical Center 
Chicago, Illinois 
Specialty: Neurosurgery, Oncology 



IX 



Barbara S. Shapiro, MD (1991-92) 

Associate Director, Pain Management Program 

Children's Hospital of Philadelphia 

Assistant Professor of Pediatrics 

University of Pennsylvania School of Medicine 

Philadelphia, Pennsylvania 

Specialties: General Pediatrics, Pain Management 

Edward B. Silberstein, MD, FACNP (1992-94) 

Associate Director, E. L. Saenger Radioisotope Laboratory 

University of Cincinnati Medical Center 

Professor of Medicine and Radiology 

University of Cincinnati College of Medicine 

Cincinnati, Ohio 

Specialties: Nuclear Medicine, Internal Medicine, 

Hematology, Oncology 

Rev. Robert S. Smith, PhD (1991-92) 

Director, Institute for Medicine in Contemporary Society 
State University Medical Center at Stony Brook 
Stony Brook, New York 
Specialty: Religion, Ethics 

Jeanne Stover (1991-92) 

Cofounder of Living Through Cancer, Inc. 
Sandia Park, New Mexico 
Consumer Representative 

Carole V. Tsou, MD (1991-92) 

Residency Program Director 
University of Hawaii 
Department of Family Practice 
Mililani, Hawaii 
Specialty: Family Medicine 

Loretta Yecchiarelli ( 1991-92) 

Rehabilitation Hospital of Western New England 
Ludlow, Massachusetts 
Consumer Representative 

David E. Weissman, MD (1992-94) 

Associate Professor of Medicine 
Division of Cancer and Blood Diseases 
Medical College of Wisconsin 
Milwaukee, Wisconsin 
Specialties: Internal Medicine, Oncology 



Acknowledgments 

The Cancer Pain Management Panel expresses profound apprecia- 
tion to the patients who helped us in the development of the consumer 
version of the guideline and to our numerous colleagues in many disci- 
plines who made valuable contributions during the development of the 
guideline. The scientific reviewers critiqued sections or complete drafts 
of the guideline document, and a variety of individuals pilot tested the 
guideline. A full listing of those involved in this effort appears in the 
list of contributors at the end of the document. Special recognition 
goes to Ehud Arbit, MD, Andrew Brown, MB BS, Stuart DuPen, MD, 
Nora Janjan, MD, Mathew Lefkowitz, MD, Margo McCaffery, RN, 
MS, Raphael Pollock, MD, PhD, Karen Syjala, PhD, Anna Williams, 
RN, MN, and Melissa Wolff, RT, MS — all of whom provided original 
text for the document. We also acknowledge the extraordinary review 
efforts of Charles Cote, MD, June Dahl, PhD, Stuart Grossman, MD, 
Philipp Lippe, MD, Margo McCaffery, RN, MS, Patricia McGrath, 
PhD, Richard Patt, MD, Vivian Sheidler, RN, MS, Thomas Smith, MD, 
and Sridhar Vasudevan, MD. These individuals provided major and 
repeated reviews of various aspects of the guideline, as well as valuable 
advice to the panel chairs. 

We acknowledge the critical approach and tireless, energetic 
efforts to the many aspects of guideline development of Jane Ballan- 
tyne, MB, Elon Eisenberg, MD, Donna Mahrenholz, RN, PhD, and 
particularly Janice Ulmer, RN, PhD, all of whom served as staff to the 
panel. Dr. Patricia Stephens provided excellent and timely editing for 
several drafts of the guideline. Research assistants who provided valu- 
able services in reviewing the literature included Dorothy Herron, 
RN, MSN, Yeonghee Shin, RN, PhD, and Joyce Willens, RN, MSN. 
Other valuable services in the preparation of various materials were 
provided by research assistants Leslie Dunham, Stella Seal, Sabreena 
Woods, and our secretary, Yvonne Deane-Hibbert, at the Johns 
Hopkins University. Drs. Frederick Mosteller, Thomas Chalmers, and 
Catherine Berkey of the Technology Assessment Group, Harvard 
School of Public Health, gave valuable guidance during literature 
reviews for meta-analyses. Miss Evelyn Hall, at Massachusetts 
General Hospital, provided expert secretarial assistance in the devel- 
opment of guideline materials. Drs. Richard Kitz and George Battit of 
the Massachusetts General Hospital provided ongoing support and 
encouragement for work at that site. 



XI 



Contents 

Executive Summary 1 

1. Overview 7 

Scope of the Problem 7 

Importance of Controlling Cancer Pain 8 

Suffering, Loss of Control, and Quality of Life 9 

Overview of Pain and Pain Management Modalities 11 

Barriers to Effective Pain Management 16 

Legal Regulation of Opioids 16 

Cost and Reimbursement for Pain Management 19 

Methods Used To Develop the Guideline 20 

Organization of Guideline 21 

2. Assessment of Pain in the Patient With Cancer 23 

Initial Pain Assessment 24 

Ongoing Pain Assessment 28 

Assessment of Common Cancer Pain Syndromes 29 

Bone Metastases 30 

Epidural Metastases/Spinal Cord Compression 30 

Metastases to the Skull 31 

Plexopathies 31 

Peripheral Neuropathies 33 

Acute and Postherpetic Neuralgia 36 

Abdominal Pain 36 

Mucositis 37 

Assessment of New Pain 38 

3. Pharmacologic Management 39 

The WHO Ladder 41 

Nonsteroidal Anti-Inflammatory Drugs (NS AIDs) 46 

Opioids 49 

Tolerance and Physical Dependence 50 

Dosage Titration 51 

Administration Methods 55 

Oral 55 

Rectal 56 

Transdermal 56 

Nasal 56 

Intravenous or Subcutaneous 57 

Intraspinal 57 

Intraventricular 59 

Patient-Controlled Analgesia (PCA) 59 

xiii 



Management of Cancer Pain 

Management of Side Effects 61 

Constipation 61 

Sedation 61 

Nausea and Vomiting 63 

Respiratory Depression 63 

Other Side Effects 64 

Adjuvant Drugs 65 

Corticosteroids 65 

Anticonvulsants 65 

Antidepressants 67 

Neuroleptic Agents 68 

Hydroxyzine 68 

Bisphosphonates and Calcitonin 69 

Placebos 69 

Antineoplastic Therapies 70 

Influence of Concurrent Medical Conditions 

on Pharmacotherapy 70 

Pharmacologic Treatments Not Recommended 71 

Discharge Planning Regarding Medications 71 

4. Nonpharmacologic Management: Physical and 

Psychosocial Modalities 75 

Introduction 76 

Physical Modalities 76 

Cutaneous Stimulation 76 

Exercise 78 

Counterstimulation 79 

TENS 79 

Acupuncture 79 

Psychosocial Interventions 80 

Relaxation and Imagery 81 

Distraction and Reframing 82 

Patient Education 83 

Psychotherapy and Structured Support 86 

Hypnosis 86 

Peer Support Groups 86 

Pastoral Counseling 87 

5. Nonpharmacologic Interventions: Invasive Therapies 89 

Introduction 90 

Radiation Therapy 90 

Bone Metastases 91 

Pain Relief With Localized Radiation Therapy 92 

Wide-Field Radiation Therapy 92 

Radiopharmaceuticals 93 

xiv 



Contents 

Plexopathy 93 

Other Therapeutic Applications 94 

Brachytherapy 94 

Anesthetic Techniques 95 

Nerve Blocks 95 

Catheter Placement for Drug Delivery 98 

Neurosurgery 99 

Neuroablation 100 

Peripheral Neurectomy 100 

Dorsal Rhizotomy 100 

Anterolateral Cordotomy (Spinal Tractotomy) 100 

Commissural Myelotomy 101 

Hypophysectomy 101 

Neuraxial Opioid Infusion 102 

Neuroaugmentation 102 

Surgery 103 

Surgical Management of Pain Due to Primary or 

Metastatic Tumor 103 

Pain as a Consequence of Operation 105 

Procedure-Related Pain in Adults and Children 107 

Managing Procedure-Related Pain 108 

Pharmacologic Strategies for Procedural Pain 108 

Sedation for Procedural Pain 112 

Additional Pain Management Strategies for 

Lumbar Puncture and Bone Marrow Aspiration 113 

Pain in Special Populations 115 

Pain in Neonates, Children, and Adolescents 116 

Assessment 117 

Methods for Assessing Pain 118 

Self-Report 118 

Behavioral Observation 119 

Pain Management 120 

Medical Interventions 120 

Analgesics and Adjuvants 120 

Analgesics for Neonates and Young Infants 124 

Epidural Analgesia 126 

Nonpharmacologic Methods 126 

Assessing the Adequacy of Pain Management Strategies . . . 127 

Elderly Patients 127 

Patients With Psychiatric Problems Associated 

With Cancer Pain 130 

Depression in Patients With Cancer Pain 131 

Suicide and Cancer Pain 132 



xv 



Management of Cancer Pain 

Anxiety 133 

Delirium and Its Effects on Treating Pain 134 

Substance Abusers 134 

Minority Populations 138 

Pain in Patients With AIDS 139 

8. Monitoring the Quality of Pain Management 143 

References 147 

Acronyms 183 

Glossary 185 

Contributors 189 

Attachment A 219 

Attachment B 227 

Attachment C 241 

Index 247 

Tables 

1. Effect of cancer pain on quality of life 11 

2. Barriers to cancer pain management 17 

3. Initial pain assessment 25 

4. Metastases to the skull 32 

5. Common cancer pain syndromes due to peripheral 

nerve injury 34 

6. Common causes of abdominal pain 36 

7. Assessment of mucositis 37 

8. Advantages and disadvantages of pain therapies 42 

9. Dosing data for acetaminophen (APAP) and NSAIDs 48 

10. Dose equivalents for opioid analgesics for opioid-naive 
adults and children ^50 kg body weight 52 

11. Dose equivalents for opioid analgesics for opioid-naive 
children and adults <50 kg body weight 54 

12. Intraspinal drug delivery systems 60 

13. General comments and cautions regarding the use of 

opioid analgesics 62 

14. Adjuvant analgesic drugs for cancer pain 66 

15. Drugs and routes of administration not recommended for 
long-term treatment of cancer pain 72 

xvi 



Contents 

16. Patient education program content 84 

17. Sources of information for patients and their families 85 

18. How to find local support groups 87 

19. Nerve blocks 95 

20. General principles of management for 

painful procedures 109 

21. Pharmacologic agents for management of 

procedural pain Ill 

22. Checklist for assessing adequacy of pain management 

in children 128 

23. Risk factors that predispose cancer patient to 

depressive disorders 132 

24. Suicide risk factors in cancer patients with pain 133 

Figures 

1. Flowchart: continuing pain management in patients 

with cancer 13 

2. The WHO three-step analgesic ladder 14 

3. Pain management strategies: a hierarchy 15 

4. Pain intensity scales 26 

5. Pain management plan 74 



xvn 



Executive Summary 

Pain control in people with cancer remains a significant problem 
in health care even though cancer pain can be managed effectively in 
up to 90 percent of patients. Recognition of the widespread under- 
treatment of cancer pain has prompted recent corrective efforts from 
health care disciplines, professional and consumer organizations, and 
governments throughout the world. 

The Clinical Practice Guideline for the Management of Cancer 
Pain was commissioned by the Agency for Health Care Policy and 
Research (AHCPR). It follows and makes reference to a 1992 guide- 
line on acute pain management after surgery or trauma, also commis- 
sioned by AHCPR. This guideline is designed to help clinicians who 
work with oncology patients to understand the assessment and treat- 
ment of pain and associated symptoms. It also discusses briefly the 
management of pain in patients with human immunodeficiency virus 
(HIV) and/or acquired immunodeficiency syndrome (AIDS). 
The guideline has ten goals: 

■ To inform clinicians and patients and their families that most 
cancer pain can be relieved by available methods. 

■ To dispel unfounded fears that addiction results from the appro- 
priate use of medications to control cancer pain. 

■ To inform clinicians that cancer pain: 
Accompanies both disease and treatment. 
Changes over time. 

May have multiple simultaneous causes. 

If unrelieved, can affect the physical, psychological, social, and 
spiritual well-being of the patient. 

■ To promote prompt and effective assessment, diagnosis, and treat- 
ment of pain in patients with cancer. 

■ To strengthen the ability of patients with cancer and their families 
to communicate new or unrelieved pain in order to secure prompt 
evaluation and effective treatment. 

■ To provide clinicians with a synthesis of the literature and expert 
opinion for application to the management of cancer pain. 

■ To familiarize patients and their families with options available for 
pain relief and to promote their active participation in selecting 
among these. 



Management of Cancer Pain 

■ To provide a model for cancer pain management to guide therapy 
in selected painful, life-threatening conditions such as AIDS. 

■ To provide information and guidelines on the use of controlled 
substances for the treatment of cancer pain that distinguish the use 
of these drugs for legitimate medical purposes from their abuse as 
illegitimate drugs. 

■ To identify health policy and research issues that affect cancer 
pain management. 

Not all cancer pain or associated symptoms can be entirely elimi- 
nated, but available approaches, when appropriately and attentively 
applied, effectively relieve pain in most patients. The importance of 
effective pain management extends beyond analgesia to encompass 
the patient's quality of life and ability to function in the family and 
society. 

Because patients vary greatly in their diagnoses and stage of 
disease progression, their responses to pain and interventions, and 
their personal preferences, the guideline offers a flexible approach to 
the management of cancer pain that clinicians can use in daily practice 
and adapt, as appropriate, to the treatment of painful noncancerous 
conditions. 

The guideline emphasizes: 

■ A collaborative, interdisciplinary approach to pain control, includ- 
ing all members of the health care team, with participation of the 
patient and the patient's family. 

■ An individualized pain control plan developed and agreed on by 
patients, their families, and practitioners. 

■ Ongoing assessment of the patient's pain. 

■ Both drug and nondrug therapies to prevent and/or control pain. 

■ A formalized, institutional approach to the management of cancer 
pain, with clear lines of responsibility for pain management and 
for monitoring the quality of pain management. 

The guideline includes general strategies for pain management, as 
well as the management of specific pain syndromes, and it addresses 
issues related to special populations. It also contains a pain manage- 
ment flowchart, analgesic dosage tables, sample pain assessment tools, 
examples of nondrug interventions, and information about resources 
for patients and their families. 

The first chapter is an overview of the prevalence of cancer and 
cancer pain. A key recommendation is that clinicians should reassure 
patients and their families that most pain can be relieved safely and 



Executive Summary 

effectively. Barriers to effective cancer pain management identified by 
the panel include problems related to health care professionals, to 
patients, and to the health care and drug regulatory system. The 
panel recommends that curricula for health professionals include 
sufficient content on pain to prepare clinicians to assess and manage 
pain effectively. The panel acknowledges that clinicians need to 
educate patients and their families about pain and its management 
and to encourage patients to be active participants in their care. Clini- 
cians are encouraged to collaborate with patients and families, taking 
costs of drugs and technologies into account in selecting pain manage- 
ment strategies. The panel noted the need for Federal, State, and local 
laws and regulatory policies to be developed so as not to hamper the 
appropriate use of opioid analgesics for cancer pain. The first chapter 
presents a flowchart that indicates the need to use multiple modalities 
concurrently in pain management and emphasizes the need to begin 
with the least invasive methods capable of controlling the pain, titrat- 
ing the pain treatment to the patient's needs. The process whereby 
panelists were selected, the methods used in the development of the 
guideline, and a summary of the scientific evidence for the interven- 
tions are presented. 

Chapter 2 emphasizes the need for health professionals to ask 
patients about pain and to accept the patient's self -report as the 
primary source of assessment. The need for comprehensive assess- 
ment and careful documentation is discussed, with attention to initial 
evaluation and appraisal of any new pain that emerges. A mnemonic 
for the recommended clinical approach is given. 

A discussion of the assessment of common cancer pain syndromes 
includes bone metastases, epidural metastases/spinal cord compres- 
sion, plexopathies, peripheral neuropathies, acute and postherpetic 
neuralgia, abdominal pain, and mucositis. 

The pharmacologic management of pain is presented in Chapter 3. 
The importance of individualizing the regimen to the patient and of 
using the simplest dosage schedules and least invasive pain manage- 
ment modalities is emphasized. The World Health Organization's 
analgesic ladder is discussed, with suggestions about how various 
drugs should be used alone and in combination. The need to make a 
distinction between opioid tolerance and physical dependence on the 
one hand and "addiction" on the other is stressed because the perva- 
sive misconception that these three entities are the same hinders 
effective pain management. 

Chapter 3 describes the use of nonsteroidal anti-inflammatory drugs 
and opioids, and discusses how to titrate drugs to effect for individual 
patients. Various routes of administration and the management of drug 
side effects are discussed. The panel noted that respiratory depression is 
infrequently a significant limiting factor in pain management because, 



Management of Cancer Pain , 

with repeated doses, tolerance develops. This tolerance allows 
adequate pain treatment without much risk of respiratory compromise. 
The person dying from cancer should not be allowed to live out life 
with unrelieved pain because of a fear of side effects; rather, appropri- 
ate, aggressive, palliative support should be given. The use of adjuvant 
drugs to increase the analgesic efficacy of opioids, to treat concurrent 
symptoms that exacerbate pain, and to provide independent analgesia 
for specific types of pain is described. Careful discharge planning when 
a patient moves from one setting to another is emphasized. 

Chapters 4 and 5 discuss the nonpharmacologic management of 
pain. Chapter 4 includes recommendations for the use of physical 
modalities, including the use of superficial heat and cold, massage, 
exercise, transcutaneous electrical nerve stimulation, and acupunc- 
ture, and psychosocial interventions, including relaxation and imagery, 
distraction and reframing, patient education, psychotherapy and struc- 
tured support, and hypnosis. For each modality, brief explanations are 
given regarding the mechanisms of operation and practical ways in 
which they can be applied in the patient care setting. The importance 
of referring patients to peer support groups and providing pastoral 
counseling for those who wish it is also emphasized. 

Chapter 5 discusses more invasive therapies, including palliative 
radiation, anesthetic techniques including nerve blocks, neurosurgery, 
and palliative surgery. The panel recommends that, with rare excep- 
tion, noninvasive treatment should precede invasive palliative 
approaches. 

Chapter 6 describes the management of procedure-related pain. It 
discusses the use of drugs and other approaches for the relief of pain 
produced by the multiple invasive procedures that patients undergo as 
part of their treatment. 

The discussion thus far in the guideline is largely focused on adult 
patients. Chapter 7 includes a discussion of a number of special popula- 
tions for whom clinicians should give special attention and considera- 
tions, including the very young and very old, the cognitively impaired, 
known or suspected substance abusers, and non-English-speaking 
persons. When developing a pain treatment plan, clinicians should be 
aware of the unique needs and circumstances of patients from various 
ethnic and cultural backgrounds. The need for assessment methods 
appropriate for neonates, children, and adolescents is stressed. Elderly 
patients should be considered at risk for undertreatment of pain. 
Uncontrolled pain is an important factor contributing to feelings of 
hopelessness, suicidal ideation, and requests for clinician-assisted 
suicide or euthanasia; therefore, it should be aggressively assessed and 
treated. Because patients with current substance abuse disorders are at 
risk for undertreatment of cancer pain, their care should be managed 
by clinicians knowledgeable in both pain management and substance 



Executive Summary 

abuse. Because patients with HIV positive/ AIDS often have pain 
problems similar to those of patients with cancer, recommendations 
for pain assessment and management in this guideline generally 
should be used for pain in these patients. 

Chapter 8 discusses the need for monitoring the quality of pain 
management and for developing formal means within each institution 
to evaluate pain management practices and to obtain patient feedback 
to gauge the adequacy of pain control. Institutional policy should 
define who is responsible for pain management, the acceptable level 
of patient monitoring, and the appropriate roles and limits of practice 
for health care providers. 

The nearly 500 consultants, peer reviewers, and site reviewers who 
contributed to the development of the guideline are listed. The 
Attachments contain tables showing the strength of evidence for 
recommendations, pain assessment instruments, and sample relax- 
ation exercises. 



Management of Cancer Pain 

Explanation of Strength of Evidence 

This guideline contains recommendations at the beginning of each 
chapter. Recommendations are followed in parentheses by a rating of 
the strength of evidence. 

When the strength of evidence is A or B, the panel's recommenda- 
tions are based primarily on the evidence. When the strength of 
recommendation is C or D, the panel used the available empirical 
evidence but based their recommendations primarily on expert judg- 
ment. When the recommendation is a statement of panel opinion 
regarding desirable practice and there is evidence that the practice is 
not commonly being followed, the term "panel consensus" is used. 

A more complete explanation of strength of evidence is contained 
in Attachment A. 



1 



Overview 



Recommendations 

1. Clinicians should reassure patients and their families that most 
pain can be relieved safely and effectively. (A) 

2. Clinicians should assess patients and, if pain is present, provide 
optimal relief throughout the course of illness. (Panel Consensus) 

3. Curricula for health professionals should include sufficient content 
on pain to prepare clinicians to assess and manage pain effectively. 
(Panel Consensus) 

4. Clinicians should include patient and family education about pain 
and its management in the treatment plan and encourage patients 
to be active participants in pain management. (A) 

5. Federal, State, and local laws and regulatory polices should not 
hamper the appropriate use of opioid analgesics for cancer pain. 
(Panel Consensus) 

6. Clinicians should collaborate with patients and families, taking 
costs of drugs and technologies into account in selecting pain 
management strategies. (Panel Consensus) 

Scope of the Problem 

Cancer is diagnosed in over 1 million Americans annually. About 
8 million Americans now have cancer or a history of cancer; half of 
these diagnoses were made within the past 5 years. Cancer causes 1 of 
every 10 deaths worldwide (Stjerasward and Teoh, 1990) and is 
increasingly prevalent in the United States, where it causes 1 of 5 
deaths-about 1,400 per day (American Cancer Society, 1994). 

Pain associated with cancer is frequently undertreated in adults 
(Bonica, 1990) and children (Miser, Dothage, Wesley, et al., 1987). 
Patients with cancer often have multiple pain problems (Coyle, 
Adelhardt, Foley, et al., 1990). Cancer pain may be due to (1) tumor 
progression and related pathology (e.g., nerve damage), (2) opera- 
tions and other invasive diagnostic or therapeutic procedures, 
(3) toxicities of chemotherapy and radiation, (4) infection, or (5) 
muscle aches when patients limit physical activity (Foley, 1979). The 
incidence of pain in patients with cancer depends on the type and 
stage of disease. At the time of diagnosis and at intermediate stages, 
30 to 45 percent of patients experience moderate to severe pain 



Management of Cancer Pain 

(Daut and Cleeland, 1982). On average, nearly 75 percent of patients 
with advanced cancer have pain. Of cancer patients with pain, 40 to 50 
percent report it as moderate to severe, and another 25 to 30 percent 
describe it as very severe (Bonica, 1990). 

In approximately 90 percent of patients, cancer pain can be 
controlled through relatively simple means (Goisis, Gorini, Ratti, et 
al., 1989; Schug, Zech, and Dorr, 1990; Teoh and Stjernsward, 1992; 
Ventafridda, Caraceni, and Gamba, 1990), yet a consensus statement 
from the National Cancer Institute Workshop on Cancer Pain indi- 
cated that the "undertreatment of pain and other symptoms of cancer 
is a serious and neglected public health problem" (National Cancer 
Institute, 1990). The Workshop concluded that "... every patient with 
cancer should have the expectation of pain control as an integral 
aspect of his/her care throughout the course of the disease" (National 
Cancer Institute, 1990). 

Because cancer pain control is a problem of international scope, the 
World Health Organization (WHO) has urged that every nation give 
high priority to establishing a cancer pain relief policy (Stjernsward and 
Teoh, 1990). In the United States, many organizations have worked 
toward this goal (Ad Hoc Committee on Cancer Pain of the American 
Society of Clinical Oncology, 1992; American Pain Society, 1986; Health 
and Public Policy Committee, American College of Physicians, 1983; 
McGivney and Crooks, 1984; Spross, McGuire, and Schmitt, 1990a, 
1990b, 1990c; Weissman, Burchman, Dinndorf, et al., 1988). 



Importance of Controlling Cancer Pain 

Pain control merits high priority for two reasons. First, unrelieved 
pain causes unnecessary suffering. Because pain diminishes activity, 
appetite, and sleep, it can further weaken already debilitated patients. 
The psychological effect of cancer pain can be devastating. Patients with 
cancer often lose hope when pain emerges, believing that pain heralds 
the inexorable progress of a feared, destructive, and fatal disease. 
Chronic unrelieved pain can lead patients to reject active treatment 
programs, and when their pain is severe or they are depressed, to 
consider or commit suicide. Besides mitigating suffering, pain control is 
important because, even when the underlying disease process is stable, 
uncontrolled pain prevents patients from working productively, enjoy- 
ing recreation, or taking pleasure in their usual role in the family and 
society (Moinpour and Chapman, 1991). Pain control therefore merits a 
high priority not only for those with advanced disease, but also for the 
patient whose condition is stable and whose life expectancy is long. 

8 



Overview 

Suffering, Loss of Control, and Quality of Life 
A Patient's Perspective: 

One of the worst aspects of cancer pain is that it's a constant 
reminder of the disease and of death. Many fear the pain will 
become unbearable before death, and those of us involved in 
support networks have seen these fears proven true. 

Pain seems greater when dealing with it alone and an increasing 
number of us are finding comfort in support groups, where we also 
deal with issues of personal control, communication with doctors 
and nurses, effective adjunctive therapies, and other topics. 

My dream is for a medication that can relieve my pain while leaving 
me alert and with no side effects. 

— Jeanne Stover, Panel Member 1991-1992 

Cancer pain may resolve with the patient's cure or continue indefi- 
nitely as a complication of otherwise curative therapy. Although 
cancer pain is often thought of as a crisis that emerges in advanced 
stages of disease, it may occur for many reasons and cause suffering, 
loss of control, and impaired quality of life throughout the patient's 
course of care, even for the patient whose condition is stable and 
whose life expectancy is long. 

Suffering denotes an extended sense of threat to self-image and 
life, a perceived lack of options for coping with symptoms or problems 
caused by cancer, a sense of personal loss, and a lack of a basis for 
hope. "Suffering can include physical pain but is by no means limited 

to it Most generally, suffering can be defined as the state of severe 

distress associated with events that threaten the intactness of the 

person The suffering of patients with terminal cancer can often be 

relieved by demonstrating that their pain truly can be controlled" 
(Cassel, 1982). 

Pain can exacerbate individual suffering by worsening helpless- 
ness, anxiety, and depression. Shock and disbelief, followed by symp- 
toms of anxiety and depression (irritability and disruption of appetite 
and sleep, inability to concentrate or carry out usual activities) are 
common when people first learn they have cancer or discover that 
treatment has failed or disease has recurred (Massie and Holland, 
1990). These symptoms usually resolve within a few weeks with 
support from family and caregivers, although medication to promote 
sleep and reduce anxiety may be necessary in crisis periods. "The 
relief of suffering and the cure of disease must be seen as twin 
obligations of a medical profession that is truly dedicated to the care 
of the sick" (Cassel, 1982). 



Management of Cancer Pain 

The obligation to alleviate suffering is an essential component of the 
clinician's broader ethical duties to benefit and not harm; it dictates 
that health professionals maintain clinical expertise and knowledge 
in the management of pain, even when present educational 
programs do not provide this. 

— Cain and Hammes, in press; Hammes and Cain, in press 

Personal control refers to an individual's ability to shape immedi- 
ate and long-range circumstances through one's own actions 
(Wallston, Wallston, Smith, et al., 1987), including: 

■ Predicting events and outcomes successfully. 

■ Exercising choice among options for action. 

■ Maintaining a repertoire of coping skills. 

■ Accessing and using relevant information. 

■ Accessing and using social or other forms of support. 

Personal control is undermined when cancer is diagnosed and is 
further reduced by ongoing pain, invasive or undignified procedures, 
treatment toxicities, hospitalization, and surgery. When pain reduces 
patients' options to exercise control, it diminishes psychological well- 
being and makes them feel helpless and vulnerable. Therefore, clini- 
cians should support active patient involvement in effective and prac- 
tical methods to manage pain. 

The quality of life of cancer patients with pain is significantly 
worse than that of cancer patients without pain (Ferrell, Rhiner, 
Cohen, et al., 1991). Table 1 depicts the effect of pain in four quality- 
of-life domains — physical, psychological, spiritual, and social. 

Family and loved ones of cancer patients share the suffering, loss 
of control, and impaired quality of life and also experience psychologi- 
cal and social stresses. Family caregivers need sleep and respite from 
the burdens of caregiving and may have socioeconomic needs and 
fears related to the costs of providing care. 

Even in the absence of psychological, emotional, and physical 
stressors, the family may feel unprepared to deal with the patient's 
many needs. They often have to assess pain, make decisions about the 
amount and type of medication, and determine when the dose of 
medication is to be given. Sophisticated pain management strategies 
may require them to manage complex medication regimens involving 
parenteral or epidural infusions in the home. 

Some family caregivers may hesitate to give adequate doses of 
pain medicines out of fear that the patient will become addicted or 

10 



Overview 
Table 1. Effect of cancer pain on quality of life 



Physical 

Decreased functional capability. 
Diminished strength, endurance. 
Nausea, poor appetite. 
Poor or interrupted sleep. 

Psychological 

Diminished leisure, enjoyment. 
Increased anxiety, fear. 
Depression, personal distress. 
Difficulty concentrating. 
Somatic preoccupation. 
Loss of control. 

Social 

Diminished social relationships. 
Decreased sexual function, affection. 
Altered appearance. 
Increased caregiver burden. 

Spiritual 

Increased suffering. 

Altered meaning. 

Reevaluation of religious beliefs. 



Source: Ferrell, Rhiner, Cohen, et al., 1991. Used with permission. 



tolerant or develop respiratory depression (Ferrell, Cohen, Rhiner, et 
al., 1991). Clinicians should reassure patients and families that most 
pain can be relieved safely and effectively. Family caregivers may feel 
unprepared to deal with a patient's need for pain relief or may deny 
that the patient is in pain to avoid facing the possibility that the 
disease is progressing. These situations require ongoing discussions 
among patients, family caregivers, and experienced health care 
providers about pain management goals. 

Overview of Pain and 

Pain Management Modalities 

The anatomy, physiology, and pharmacology of pain and analgesia 
have been studied extensively. A major advance has been the finding 
that neural pathways that arise in the brain stem descend to the spinal 
cord and modulate activity in spinal nociceptive pathways (Fields and 

11 



Management of Cancer Pain 

Basbaum, 1978). These descending pathways, as well as related pain 
pathways within and above the spinal cord, respond to opioids and 
other analgesic drugs as well as physiologic and experimental stimuli, 
including stress (Mayer and Liebeskind, 1974), to produce analgesia. 
It has been speculated that the activation of this descending control 
system by the action of endogenous opioids such as (3-endorphin and 
enkephalins may account for the phenomenon of placebo analgesia 
and the apparent analgesic effect of acupuncture in some clinical 
circumstances. 

Pain may be defined as "an unpleasant sensory and emotional 
experience associated with actual or potential tissue damage, or 
described in terms of such damage" (International Association for the 
Study of Pain, Subcommittee on Taxonomy, 1979). Although the 
mechanisms of pain and pain pathways are becoming better under- 
stood, it should be emphasized that an individual's perception of pain 
and appreciation of its meaning are complex phenomena that involve 
psychological and emotional processes in addition to activation of 
nociceptive pathways (McGrath, 1990a). Pain intensity is not propor- 
tional to the type or extent of tissue damage but may be influenced at 
many sites within the nervous system. The perception of pain depends 
on the complex interactions between nociceptive and non-nociceptive 
impulses in ascending pathways, in relation to the activation of 
descending pain-inhibitory systems. This framework provides the 
basis for a comprehensive, multimodal approach to the assessment 
and treatment of patients with pain and fits with the clinical observa- 
tion that there is no single approach to effective pain management. 
Instead, individualized pain management should take into account the 
stage of disease, concurrent medical conditions, characteristics of pain, 
and psychological and cultural characteristics of the patient. It also 
requires ongoing reassessment of the pain and treatment effectiveness. 

Figure 1 is a flowchart depicting cancer pain management from 
the initial assessment of pain and its cause to the various treatment 
modalities, including the WHO analgesic ladder and numerous other 
drug and non-drug modalities (World Health Organization, 1990). The 
best choice of modality often changes as the patient's condition and 
the characteristics of the pain change. It is important that the effec- 
tiveness of analgesic modalities used separately or in combination be 
carefully assessed. The flowchart indicates the complexity of both the 
sources of pain and the types of modalities available for managing it. 
This guideline elaborates on the modalities, making recommendations 
about their appropriate use. Whenever pain is present, clinicians 
should provide optimal pain relief by routinely assessing pain and 
treating it with one or more of the modalities described here. 

The WHO ladder (Figure 2) portrays a progression in the doses and 
types of analgesic drugs for effective pain management. When this 

12 



Figure 1. Flowchart: Continuing pain management 
in patients with cancer 



Pain unrelated 
to cancer 



I 



Treat according to 
source of pain 



Add as indicated: 

Palliative therapies 

• Radiation therapy 

• Surgery 

• Nerve blocks 

• Antineoplastic therapy 
Adjuvant drugs 

Psychosocial 
interventions 
Physical modalities 



Unacceptable 
side effects 

Use different 
drugs or 
change 
route of 
administration 

Manage side 
effects 

• Adjuvant 
drugs 

• Cognitive 
behavioral 
modalities 



Diffuse 
bone pain 

Optimize 
NSAID and 
opioid doses 

Radio- 
pharma- 
ceuticals 

Bisphos- 
phonates 

Hemibody 
therapy 

Hypophy- 
sectomy 



Assessment 



I 



Cancer pain 



No pain —I 



Initiate 
analgesic ladder 



Reassessment 



Pain relief 

Continue treatment 
as needed 



Pain persists 



Consider other 

etiologies and 

treatments 



Neuropathic pain 

(Peripheral 
neuropathies, 
plexopathies, 
spinal cord 
compression) 

Adjuvant drugs 

Opioids titrated 
to effect 

Radiation therapy 

Spinal opioids 
with local 
anesthetics for 
intractable lower 
body pain 

Neurolytic 
procedures 



Reassessment 



Movement- 
related pain 

Surgical or 
physical 
stabilization of 
affected part 

Nerve blocks 

Neuroablative 
surgery and 
neurolytic 
procedures 



1 



Mucositis 

Oral 
mouth- 
washes and 
local 

anesthetic 
rinses 

Opioids 

• Transdermal 

• Patient 
controlled 
analgesia, 
intravenous, 
and sub- 
cutaneous 

Antibiotics 



13 



Management of Cancer Pain 

noninvasive approach is ineffective, alternative modalities include other 
routes of drug administration, nerve blocks, and ablative neurosurgery 
(Figure 3). As Figure 3 indicates, patients receiving treatments of vary- 
ing degrees of invasiveness may also benefit from other modalities; the 
number of patients receiving these modalities either separately or in 
combination has not been well documented. The estimates presented 
in Figure 3 reflect various clinical populations and may not represent 
all settings and populations; furthermore, they do not necessarily 

Figure 2. The WHO three-step analgesic ladder 




Source: World Health Organization, 1990. Used with permission. 



14 



Overview 



Figure 3. Pain management strategies: a hierarchy 




Consultants' estimates 
of prevalence of use 
of progressively 
more invasive therapies 

Nerve blocks, 
palliative surgery, 
and ablative surgery, 

1-5%. 1 



□ 



□ 



Epidural and 

intrathecal 

analgesics, 

2-6%. 2 

Intravenous and 
subcutaneous drugs, 
5-20%. 3 



Oral, transdermal, 
and rectal drugs, 
75-85%. 4 



1 Hiraga, Mizuguchi, and Takeda, 1991; Portenoy, 1993; Ventafridda, Caraceni, and 

Gamba, 1990. 

2 Hiraga, Mizuguchi, and Takeda, 1991; Ventafridda, Caraceni, and Gamba, 1990. 

3 Keller, 1984; Paice, 1993; Portenoy, 1993. 

4 Goisis, Gorini, Ratti, et al., 1989; Hiraga, Mizuguchi, and Takeda, 1991; Scug, Zech, and 

Dorr, 1990; Takeda, 1986; Ventafridda, Caraceni, and Gamba, 1990; Walker, Hoskin, Hanks, 

etal., 1988. 

Note: The pyramid depicts a hierarchy of pain management strategies from least invasive (at 
the base) to most invasive (at the apex). Therapies depicted on the ribbon may benefit many 
patients who are receiving concurrent treatments at any level of invasiveness. Estimates 
presented in the sidebar are based on published data and consultants' estimates for various 
clinical populations in industrialized nations but may not reflect all settings and do not neces- 
sarily reflect what is optimal. 



15 



Management of Cancer Pain 

reflect what is optimal, but only a range of current opinions. There is a 
need for research to determine the effectiveness of many of these 
modalities used alone or in combination for different patient popula- 
tions in various settings. 

Barriers To Effective Pain Management 

Pain management is often needlessly suboptimal (Table 2). Health 
care professionals are seldom trained in pain management, may not 
realize the importance of pain management or recognize that a patient 
is in pain, and may fear prescribing opioid medications. 

Like some clinicians, patients and families may shun the use of 
opioids and, because of their fears of addiction and worries about 
tolerance, may not complain about pain or about poor pain relief. 
Therefore, the panel recommends that clinicians include patient and 
family education about pain and its management in the treatment plan. 

Another barrier is that pain management has not traditionally 
been a priority of the health care system. Pain treatment may not be 
reimbursed or readily accessible, and institutions may be more 
concerned about a patient's possible opioid addiction or the diversion 
of controlled substances than about optimizing pain relief. Clinicians 
should reassure patients who are reluctant to report pain and who fear 
addiction and unmanageable side effects that there are many ways to 
relieve pain safely and effectively. Talking with clinicians knowledge- 
able about pain management and reading the consumer versions of 
this guideline (Jacox, Carr, Payne, et al., 1994, in press) should help 
patients and their families to overcome fears and concerns that hinder 
effective pain relief. 

Problems related to the health care system and suggestions for 
resolving these are addressed extensively elsewhere (Angarola and 
Wray, 1989; Cain and Hammes, in press; Cleeland, Cleeland, Dar 
et al., 1986; Cleeland, 1987; Ferrell and Griffith, in press; Hammes and 
Cain, in press; Hill, 1993; Joranson, in press; Kolassa, in press; Shapiro, 
in press, a, b). Two of the problems — restrictive regulation of controlled 
substances and reimbursement policies — are discussed briefly here. 

Legal Regulation of Opioids 



The Federal government attempts to ensure the availability of 
opioid analgesics for legitimate medical and scientific purposes while 
controlling the abuse and illegal diversion of such substances 
(Shapiro, in press, a). The Controlled Substances Act (CSA) is one of 
the principal Federal laws that affects the use and availability of 
controlled substances, including opioid analgesics. The CSA provides 
for the registration of all handlers of controlled substances, as well as 

16 



Overview 
Table 2. Barriers to cancer pain management 

Problems related to health care professionals 

Inadequate knowledge of pain management. 1 

Poor assessment of pain. 2 

Concern about regulation of controlled substances. 3 

Fear of patient addiction. 4 

Concern about side effects of analgesics. 5 

Concern about patients becoming tolerant to analgesics. 6 

Problems related to patients 

Reluctance to report pain. 7 

Concern about distracting physicians from treatment of underlying disease. 

Fear that pain means disease is worse. 

Concern about not being a "good" patient. 
Reluctance to take pain medications. 8 

Fear of addiction or of being thought of as an addict. 

Worries about unmanageable side effects. 

Concern about becoming tolerant to pain medications. 

Problems related to the health care system 

Low priority given to cancer pain treatment. 9 
Inadequate reimbursement. 10 

The most appropriate treatment may not be reimbursed or may be too 

costly for patients and families. 
Restrictive regulation of controlled substances. 11 
Problems of availability of treatment or access to it. 12 



1 Bonica, 1985; Cleeland, Cleeland, Dar, et al., 1986; Ferrell, Cronin Nash, and Warfield, 1992; 

Von Roenn, Cleeland, Gonin, et al., 1993. 

2 Grossman, Sheidler, Swedeen, et al., 1992; Von Roenn, Cleeland, Gonin, Hatfield, 

etal., 1993. 

3 Joranson, Cleeland, Weissman, et al., 1992; Shapiro, in press, a, b; Von Roenn, Cleeland, 

Gonin, et al., 1993; Weissman, Joranson, and Hopwood, 1991. 

4 Bonica, 1985; Ferrell, Cronin Nash, and Warfield, 1992; Marks and Sachar, 1973. 

5 Cleeland, Cleeland, Dar, et al., 1986; Von Roenn, Cleeland, Gonin, et al., 1993. 

6 Cleeland, Cleeland, Dar, et al., 1986; Shapiro, in press, a, b. 

7 Dar, Beach, Barden, et al., 1992; Levin, Cleeland, and Dar, 1985; Von Roenn, Cleeland, 

Gonin, et al., 1993; Ward, Goldberg, Miller-McCauley, et al., 1993. 

8 Cleeland, 1989; Dar, Beach, Barden, et al., 1992; Hodes, 1989; Joranson, in press; Levin, 

Cleeland, and Dar, 1985; Rimer, Levy, Keintz, et al., 1987; Von Roenn, Cleeland, Gonin, et al., 

1993; Ward, Goldberg, Miller-McCauley, et al., 1993. 

9 Bonica, 1985; Max, 1990. 

10 Ferrell and Griffith, in press; Joranson, in press. 

11 Foley, 1985a; Joranson, Cleeland, Weissman, et al., 1992; Shapiro, in press, a, b; Weissman, 
Joranson, and Hopwood, 1991. 

12 Foley, 1985a. 



17 



Management of Cancer Pain 

for the labeling, order forms, recordkeeping, and reporting of 
substances or their use. These activities enable enforcement agencies 
to identify manufacturers, distributors, clinicians, and pharmacists 
who divert controlled substances for illicit uses. The CSA also 
includes provisions that explicitly aim to avoid interference with the 
availability of U.S. Food and Drug Administration (FDA)-approved 
drugs for legitimate purposes. The CSA does not restrict a clinician's 
medical decision about which drug to prescribe, in what amounts, or 
for what duration, although it does prohibit physicians from prescrib- 
ing opioids to maintain narcotic addiction unless the physician is sepa- 
rately registered to treat addiction. "Addict" is defined in the CSA as 
one who habitually uses an opioid drug so as to endanger public 
health or safety or one who has lost control over opioid use 
(Controlled Substances Act, 21 U.S.C., sec. 802). This definition rarely 
applies to a patient being treated with opioids for cancer pain (Kanner 
and Foley, 1981). Furthermore, Federal controlled substances regula- 
tions clarify that the Federal law is not intended to impose limitations 
on a physician's ability to prescribe opioid analgesics to persons with 
intractable pain in situations where no relief or cure is possible or 
none has been found after reasonable efforts (21 CFR 1306.07(c)). 

State laws vary greatly, and many restrict or regulate the prescribing 
of opioids in the treatment of pain in ways that Federal law does not. 
For example, many State drug diversion laws contain ill-defined terms 
that in effect restrict opioid prescribing (Joranson, 1990). Other State 
laws also regulate pain treatment by restricting medication prescriptions 
to a specific number of dosage units or to a 1 -month supply, or by moni- 
toring the prescription of controlled substances through multiple-copy 
prescription programs. WHO has observed that although multiple-copy 
prescription programs are intended to reduce careless prescribing, 
"Health care workers may be reluctant to prescribe, stock or dispense 
opioids as they feel that there is a possibility of their professional 
licenses being suspended or revoked by the governing authority in cases 
where large quantities of opioids are provided to an individual, even 
though the medical need for such drugs can be proved" (World Health 
Organization, 1990). In States with formal cancer pain initiatives, health 
professionals have worked with State agencies to identify and remove 
legal impediments to the use of controlled substances for cancer pain 
(Dahl, Joranson, Engber, et al., 1988). 

A 1990 revision of the Uniform Controlled Substances Act 
addresses the legitimate use of controlled substances by recognizing 
that the prescribing, administering, and dispensing of opioid anal- 
gesics for intractable pain is part of professional medical treatment. It 
states that if terms such as addict, habitual user, and drug-dependent 
person are used in States' statutes, definitions of these terms should 
clearly indicate that they do not apply to patients receiving controlled 

18 



Overview 

substances pursuant to a practitioner's order (Uniform Controlled 
Substances Act, 1990). Each State legislature has received the revision 
from the Uniform Law Commissioners. 

The panel recommends that laws and regulatory policies aimed at 
diversion control not hamper the appropriate use of opioid analgesics 
for cancer pain. Clinicians are responsible for knowing how controlled 
substances are regulated in their States. Such information can be 
obtained from State medical, nursing, and pharmacy licensing boards 
(see Angarola, 1990; Joranson, 1990; Shapiro, in press, a, for addi- 
tional information on the regulation of analgesic drugs). 

Cost and Reimbursement for Pain Management 



Determining the overall cost of pain management is difficult 
because it generally is not separated from other treatment costs, but 
rather is included as part of the patient's stay in the hospital or an outpa- 
tient visit. Components of pain management costs and a comparison of 
analgesic drug costs are discussed by Ferrell and Griffith (in press) 
and Kolassa (in press). 

Access to professional services, prescription drugs, and medical 
equipment is usually necessary for effective pain care (Joranson, in 
press). Reimbursement or lack of it influences the way in which pain is 
treated, where it is treated, and the supportive care that is available 
(Yasco and Verfurth, 1992). Reimbursement policies of third-party 
payers for pain management differ substantially, and many people 
with cancer are uninsured or underinsured. According to one report 
(American Cancer Society, 1989), low-income people experience 
greater pain and suffering from cancer than do other Americans, and 
a disproportionate share of people with little or no insurance are 
minorities. For those who are insured, reimbursement policies may 
favor the use of more expensive pain management modalities over 
less expensive ones. Medicare, for example, does not reimburse for 
outpatient oral analgesics but will reimburse for pain management in 
an inpatient facility. Thus, "a person may well have reimbursement for 
the $4,000.00 cost of patient controlled analgesia (PCA) morphine but 
will have no coverage for $100.00 of oral morphine solution" (Ferrell 
and Griffith, in press). Joranson (in press) has reported on the varia- 
tion in the policies of private payers and health maintenance organiza- 
tions, in which policies are often unclear about or offer minimal cover- 
age for pain management. Reimbursement policies on pain 
management should be studied to enable further understanding of 
those that promote the most cost effective pain management. 

Clinicians should consider a patient's ability to pay for treatment. 
The costs of medication and other treatments may overburden a 

19 



Management of Cancer Pain 

patient with limited financial resources and result in compromises 
between adherence to the prescribed regimen and other financial 
responsibilities (Brand, Smith, and Grand, 1977). Costs of analgesic 
drugs, for example, including many that are equally effective for pain 
management, vary dramatically (Kolassa, in press). For example, an 
analysis of the costs of NSAIDs included in the drug tables of this 
guideline showed that the retail price of NSAIDs (excluding aceta- 
minophen and aspirin) in 1992 ranged from $10.50 to $127.80 for a 30- 
day supply (Kolassa, in press). Although the primary concern of the 
clinician is to manage pain effectively, the ability to do this may be 
influenced by the patient's economic status. Therefore, clinicians 
should collaborate with patients and families, taking cost of drugs and 
technologies into account when selecting pain management strategies. 

Methods Used To Develop the Guideline 

This guideline was developed by an interdisciplinary, expert panel, 
commissioned by AHCPR, that comprises practitioners in nursing, 
medicine, pharmacy, psychology, and physical therapy; health care 
consumers; and an ethicist. 

The panel used four processes to develop the guidelines. First, it 
undertook an extensive and interdisciplinary clinical review of current 
needs, therapeutic practices and principles, and emerging technologies 
for cancer pain control. This process included a review of all pertinent 
guidelines and standards, the solicitation of information and opinions 
from external consultants, and an open forum (announced in the 
Federal Register and held in Washington, DC, on September 5, 1991) 
to receive the broadest possible input from concerned parties. 

Second, the panel performed a comprehensive scientific review of 
the field to define the existing knowledge base and evaluate critically 
the assumptions and common wisdom in the field. Although the 
primary focus of the review was on cancer pain, the panel also 
reviewed the pain literature on HIV positive/AIDS. When there were 
few studies available that tested the use of interventions with various 
populations of cancer patients, studies conducted on other clinical 
populations were used as supplementary scientific evidence. The 
panel examined studies on patients of all ages. It performed a best- 
evidence synthesis of the scientific evidence, including a meta-analysis 
when sufficient numbers of experimental studies were found in the 
literature. Nineteen data bases were searched, and approximately 
9,600 citations were screened. Six hundred twenty-five research stud- 
ies were critiqued for scientific merit, and 550 were included in tables 
of evidence for the various interventions. 

Attachment A gives ratings of strength of the scientific evidence 
for interventions, along with the types and ratings for evidence of the 

20 



Overview 

specific interventions included in the guidelines. Briefly, the strength 
and consistency of evidence for recommendations describes the 
evidence and notes whether it is generally consistent or inconsistent. 
Strength of evidence ranges from A (strongest) to D (little or no 
systematic empirical evidence). 

When the strength of evidence is A or B, the panel's recommenda- 
tions are based primarily on the evidence. When the strength of 
recommendation is C or D, the panel used the available empirical 
evidence but based their recommendations primarily on expert judg- 
ment. When the recommendation is a statement of panel opinion 
regarding desirable practice and there is evidence that the practice is 
not commonly being followed, the term "panel consensus" is used. 

Third, guideline drafts were developed by members of the panel, 
consultants, and panel staff. In all, 17 drafts were written. 

Fourth, the panel initiated peer review of two drafts of the guide- 
line and field tested a draft with intended users in clinical sites. 
Comments were reviewed and incorporated into the final guideline. 
The patient brochure was developed by panel members and field 
tested with 69 patients and six clinicians. 

Four hundred sixty-eight consultants, peer reviewers, and site 
testers reviewed and contributed to the development of the guideline. 
The entire process was anchored by the panel, which met six times 
over a period of 2 years. 

Organization of Guideline 

Users of this guideline can easily refer to sections of immediate 
interest. It begins with a discussion of pain assessment and then 
presents methods of pain control. These methods appear in separate 
sections dealing with the pharmacologic management of pain, the use 
of psychosocial and physical modalities, and the use of anesthetic and 
surgical interventions and radiation therapy. One chapter discusses 
procedure-related pain in adults and children. Another addresses pain 
in special populations, including infants and children, the elderly, 
known or suspected substance abusers, minorities, HIV positive/AIDS 
patients, and people with psychiatric problems. The final section 
discusses institutional responsibility for effective pain management. 
Attachment A contains tables of scientific evidence for the interven- 
tions. Attachment B contains pain assessment instruments for adults 
and children. Attachment C includes sample relaxation exercises. A 
glossary, as well as lists of consultants, peer reviewers, and site testers 
of the guideline are also provided. To derive maximal benefit, clini- 
cians should read the entire guideline. 



21 



2 



Assessment of Pain in the 
Patient With Cancer 



Recommendations 

7. Health professionals should ask about pain, and the patient's self- 
report should be the primary source of assessment. (B) 

8. Clinicians should assess pain with easily administered rating scales 
and should document the efficacy of pain relief at regular intervals 
after starting or changing treatment. Documentation forms should 
be readily accessible to all clinicians involved in the patient's care. 
(Panel Consensus) 

9. Clinicians should teach patients and their families to use assess- 
ment tools in their homes in order to promote continuity of effec- 
tive pain management across all settings. (Panel Consensus) 

10. The initial evaluation of pain should include: 

■ A detailed history, including an assessment of pain intensity 
and characteristics. 

■ A physical examination. 

■ A psychosocial assessment. 

■ A diagnostic evaluation of signs and symptoms associated with 
the common cancer pain syndromes. (Panel Consensus) 

11. Clinicians should be aware of common pain syndromes: this 
prompt recognition may hasten therapy and minimize the morbid- 
ity of unrelieved pain. (B) 

12. Changes in pain patterns or the development of new pain should 
trigger a diagnostic evaluation and modification of the treatment 
plan. (Panel Consensus) 

Assessment of pain in the cancer patient is imperative for all 
health care professionals because failure to assess pain can lead to its 
undertreatment. The critical role of the assessment of cancer pain was 
highlighted in a 1993 study of 897 oncologists who, collectively in the 
previous 6 months, had managed more than 70,000 cancer patients. 
According to these physicians, poor pain assessment was the greatest 
barrier to effective cancer pain management in their own practices 
(Von Roenn, Cleeland, Gonin, et al., 1993). Because of the multiple 
possible causes of pain, careful evaluation of pain is required. 

23 



Management of Cancer Pain . 

Initial Pain Assessment 

The initial assessment should occur with each new report of pain 
and should focus on identifying the cause of the pain and developing a 
pain management plan. Subsequent assessments should evaluate the 
effectiveness of the plan and, if pain is unrelieved, determine whether 
the cause is related to the progression of disease, a new cause of pain, 
or the cancer treatment. 

The initial evaluation of pain should include: 

■ Detailed history, including an assessment of the pain intensity 
and character. 

■ Physical examination, emphasizing the neurologic examination. 

■ Psychosocial assessment. 

■ Appropriate diagnostic workup to determine the cause of the pain. 

Attention to detail is important: a delayed or incorrect diagnosis, 
particularly with a syndrome such as spinal cord compression, can 
result in increased morbidity, needless pain and suffering, or both. The 
initial assessment should provide a detailed description of each type of 
pain (Table 3). 

Health professionals should ask about pain, and the patient's self- 
report should be the primary source of assessment. The self-report 
should include a description of the pain; its location, intensity/severity, 
and aggravating and relieving factors; and the patient's cognitive 
response to pain. Neither behavior nor vital signs should be used in 
lieu of a self-report (Beyer, McGrath, and Berde, 1990). It is best to 
use brief, easy-to-use assessment tools that reliably document pain 
intensity and pain relief and to relate these to other dimensions of 
pain such as mood. (Examples of both brief and comprehensive pain 
inventories are included in Attachment B.) One routine clinical 
approach to pain assessment and management is summarized by the 
mnemonic "ABCDE": 

A Ask about pain regularly. 

Assess pain systematically. 

B Believe the patient and family in their reports of pain and what 
relieves it. 

C Choose pain control options appropriate for the patient, family, 
and setting. 

D Deliver interventions in a timely, logical, and coordinated fashion. 

E Empower patients and their families. 

Enable them to control their course to the greatest extent possible. 

24 



Table 3. Initial pain assessment 



A. Assessment of pain intensity and character 

1 . Onset and temporal pattern — When did your pain start? How often does it 
occur? Has its intensity changed? 

2. Location — Where is your pain? Is there more than one site? 

3. Description — What does your pain feel like? What words would you use to 
describe your pain? 

4. Intensity— On a scale of to 1 0, with being no pain and 1 being the 
worst pain you can imagine, how much does it hurt right now? How much 
does it hurt at its worst? How much does it hurt at its best? 

5. Aggravating and relieving factors — What makes your pain better? What 
makes your pain worse? 

6. Previous treatment — What types of treatments have you tried to relieve 
your pain? Were they and are they effective? 

7. Effect — How does the pain affect physical and social function? 

B. Psychosocial assessment 

Psychosocial assessment should include the following: 

1 . Effect and understanding of the cancer diagnosis and cancer treatment on 
the patient and the caregiver. 

2. The meaning of the pain to the patient and the family. 

3. Significant past instances of pain and their effect on the patient. 

4. The patient's typical coping responses to stress or pain. 

5. The patient's knowledge of, curiosity about, preferences for, and expecta- 
tions about pain management methods. 

6. The patient's concerns about using controlled substances such as opioids, 
anxiolytics, or stimulants. 

7. The economic effect of the pain and its treatment. 

8. Changes in mood that have occurred as a result of the pain (e.g., depres- 
sion, anxiety). 

C. Physical and neurologic examination 

1 . Examine site of pain and evaluate common referral patterns. 

2. Perform pertinent neurologic evaluation. 

■ Head and neck pain — cranial nerve and fundoscopic evaluation. 

■ Back and neck pain — motor and sensory function in limbs; rectal and 
urinary sphincter function. 

D. Diagnostic evaluation 

1 . Evaluate recurrence or progression of disease or tissue injury related to 
cancer treatment. 

■ Tumor markers and other blood tests. 

■ Radiologic studies. 

■ Neurophysiologic (e.g., electromyography) testing. 

2. Perform appropriate radiologic studies and correlate normal and abnormal 
findings with physical and neurologic examination. 

3. Recognize limitations of diagnostic studies. 

■ Bone scan — false negatives in myeloma, lymphoma, 
previous radiotherapy sites. 

■ CT scan — good definition of bone and soft tissue but 
difficult to image entire spine. 

■ MRI scan — bone definition not as good as CT; better images of spine 
and brain. 



25 



Management of Cancer Pain 

In the initial assessment, document the onset and temporal pattern 
of the pain. Ask patients to point to the exact location of the pain on 
themselves or the clinician (The Brief Pain Inventory and the Initial 
Pain Assessment Tool in Attachment B). Determine whether the pain 
radiates or spreads to other parts of the body. 

Ask patients to describe their pain: the descriptive words they use 
can provide valuable clues as to the cause. For example, patients who 
describe back pain that radiates like a tight band around their chest 
and worsens with coughing or defecation should be evaluated for 
potential spinal cord compression, a complication of vertebral body 
metastasis. Patients who describe their pain as "burning" or "tingling" 
are likely to have a neuropathic cause of pain — particularly when it is 
associated with subjective numbness, loss of sensation, and weakness 
(Elliott and Foley, 1989). 

Three commonly used self-report assessment tools (Figure 4) are: 

■ Simple Descriptive Pain Intensity Scale. 

■ 0-10 Numeric Pain Intensity Scale. 

■ Visual Analog Scale (VAS). 

Figure 4. Pain intensity scales 

Simple Descriptive Pain Intensity Scale 1 

I 1 1 1 1 1 

No Mild Moderate Severe Very Worst 

pain pain pain pain severe possible 

pain pain 

0-10 Numeric Pain Intensity Scale 1 

I — I — I — I — I — I — I — I — I — I — I 

0123456789 10 

No Moderate Worst 

pain pain possible 

pain 

Visual Analog Scale (VAS) 2 



No Pain as bad 

pain as it could 



possibly be 



1 lf used as a graphic rating scale, a 10 cm baseline is recommended. 
2 A 10-cm baseline is recommended for VAS scales. 



Source: Acute Pain Management Guideline Panel, 1992. 
26 



Pain Assessment 

If the patient understands the scale and is capable of answering 
and if end points and adjective descriptors are carefully selected, each 
of these instruments can be valid and reliable (Gracely and Wolskee, 
1983; Houde, 1982; Sriwatanakul, Kelvie, and Lasagna, 1982). 

An assessment of pain intensity should include an evaluation of 
not only the present pain intensity but also pain at its least and worst. 
Knowing factors that aggravate or relieve pain helps clinicians to 
design a pain treatment plan. The initial pain assessment should elicit 
information about changes in activities of daily living, including work 
and recreational activities, sleep patterns, mobility, appetite, sexual 
functioning, and mood. 

A psychosocial assessment should emphasize the effect of pain on 
patients and their families, as well as patients' preferences among pain 
management methods. Patients who are able to answer should be 
asked about the effectiveness of past and present pain treatments, 
such as antineoplastic therapy or specific pharmacologic and nonphar- 
macologic therapies. 

The clinician should perform a physical and neurologic examina- 
tion related to the pain report (see below, Assessment of Common 
Cancer Pain Syndromes). The painful area should be carefully exam- 
ined to determine if palpation or manipulation of the site exacerbates 
the pain. Common sites of pain referral should be evaluated (e.g., 
shoulder pain may emanate from subdiaphragmatic abdominal 
sources; knee and hip pain may be referred from lumbar spine 
lesions). In addition, the patient should be observed for cues that indi- 
cate pain, e.g., distorted posture, impaired mobility, guarding the 
painful area, restricted movement of a limb, anxiety, attention seeking, 
or depression. However, absence of these behaviors should not be 
interpreted to mean that the patient has no pain. 

Neurologic examination should be focused. For example, pain in 
the head and neck region requires careful cranial nerve examination 
to exclude intracranial pathology and lesions at the base of the skull, 
that may require definition by specialized magnetic resonance imaging 
(MRI) or computed tomography (CT). Neck or back pain require 
careful motor, sensory, and reflex examination of the arms and legs, as 
well as evaluation of rectal and urinary sphincter function to exclude 
plexopathy and spinal cord lesions. 

Appropriate diagnostic tests should be performed to determine 
the cause of the pain and the extent of disease, and patients should be 
offered analgesia to facilitate these evaluations (e.g., to allow the 
patient to lie flat for CT or MRI scans). It is important to correlate the 
results of these studies with physical and neurologic findings to assure 
that appropriate areas of the body have been imaged and that identi- 
fied abnormalities do in fact explain the patient's pain. Pain may be 
the first sign of tumor recurrence or progression and may appear or 

27 



Management of Cancer Pain , 

increase before changes are evident in imaging studies; therefore, 
imaging studies may have to be repeated. 

Ongoing Pain Assessment 

The assessment of the patient's pain and the efficacy of the treat- 
ment plan should be ongoing, and the pain reports should be docu- 
mented. Simply to record a patient's responses to the question "How 
is your pain?" invites misunderstanding and hinders quantification. 

Pain should be assessed and documented: 

■ At regular intervals after starting the treatment plan. 

■ With each new report of pain. 

■ At a suitable interval after each pharmacologic or nonpharmaco- 
logic intervention, such as 15 to 30 minutes after parenteral drug 
therapy and 1 hour after oral administration. 

Occasionally, discrepancies between behaviors and a patient's self- 
report of pain may occur. For example, patients may describe pain as 
an 8, on a scale of to 10, while smiling and walking freely, or con- 
versely, as a 2 while experiencing tachycardia, splinting, and sweating, 
although this is less usual. These discrepancies may result from several 
factors, including the effectiveness of the patient's coping skills (see 
Chapter 4). The patient who uses distraction and relaxation techniques 
may engage in diversionary activities while still experiencing severe 
pain; in fact, this is a goal of many behavioral pain therapies. Patients 
may deny severe pain for a variety of reasons, including a perception 
that stoicism is expected or rewarded or a fear that the pain symbol- 
izes disease progression. Similarly, patients managed with as-needed 
analgesia may perceive that medication will be given only if the pain 
score is very high. When discussing pain assessment and control with 
patients, members of the health care team should emphasize the 
importance of a factual report, thereby avoiding both stoicism and 
exaggeration. If anxiety or other concerns are significant, patients 
should be asked to rate their emotional distress separately from their 
pain, using similar scales (see Pain Distress Scales in Attachment B). 
They also may be asked to rate their mood or the effectiveness of 
analgesic therapies (see the Memorial Pain Assessment Card in 
Attachment B). When discrepancies between behaviors and self- 
reports of pain occur, these differences should be discussed with the 
patient, and the pain management plan should then be revised. 

28 



Pain Assessment 

Most cancer patients are treated for pain in outpatient and home 
care settings. Plans should be made to ensure ongoing assessment of 
the pain and the effectiveness of treatments in these settings. Patients 
can keep a log of their pain intensity scores and report these scores 
during followup visits or through telephone followup. In addition, 
patients should be taught to report changes in their pain or any new 
pain so that appropriate reassessment and changes in the treatment 
plan can be initiated. 

Patients unable to communicate effectively with staff require 
special consideration (see Chapter 7). Even patients previously able to 
communicate may be unable to do so as their disease progresses. 
Aggressive efforts should be made to find a translator for the non- 
English-speaking patient to determine a convenient way to assess 
pain. Many of the pain assessment tools have already been translated 
(Beyer and Wells, 1993; Cleeland and Syrjala, 1992). 

When developing a treatment plan, members of the health care 
team should pay particular attention to the preferences and needs of 
patients whose education or cultural traditions may impede effective 
communication (see Chapter 7 for additional discussion). Certain 
cultures have strong beliefs about pain and its management, and 
members of these cultures may hesitate to report unrelieved pain or 
may have specific preferences for pain-relieving measures. When 
developing a treatment plan, clinicians should be aware of the unique 
needs and circumstances of patients from different age groups or vari- 
ous ethnic and cultural backgrounds. 



Assessment of Common Cancer Pain Syndromes 

Patients can experience acute or chronic pain from their cancer, 
diagnostic procedures, treatment, or preexisting conditions. Thus, 
patients should be carefully assessed to ensure that the cause of pain is 
established whenever possible and treated appropriately. 

Some causes of cancer pain are relatively easy to diagnose and 
treat (e.g., pathologic fractures). However, clinicians treating patients 
with cancer should also be able to recognize readily the common pain 
syndromes that may cause intractable pain and that may signal disease 
recurrence in order to optimize therapy and minimize the morbidity 
of unrelieved pain. Furthermore, because many intractable pain prob- 
lems involve neurologic structures (e.g., epidural spinal cord compres- 
sion; metastatic brachial and lumbosacral plexopathy), prompt recog- 
nition and treatment of these syndromes may also minimize neurologic 
impairment (Elliott and Foley, 1989). 

29 



Management of Cancer Pain 
Bone Metastases 



Multiple myeloma and cancers of the breast, prostate, and lung 
account for a large majority of bone metastases. The most common 
sites of bone metastasis include the vertebrae, pelvis, femur, and skull. 
Distal extremity metastases are uncommon (Malawer and Delaney, 
1989). The most frequent symptom is pain, although 25 percent of 
patients with bone metastases have no symptoms (Wagner, 1984). Pain 
may result from direct tumor involvement of bone with activation of 
local nociceptors, or compression of adjacent nerves, vascular struc- 
tures, and soft tissue. Because patients often have multiple sites of 
bone metastases, multiple areas of pain are common. Pain is usually 
described as dull and aching, is usually localized to the area of metas- 
tasis, and is increased by movement. However, spine metastases may 
impinge upon nerve roots and result in radicular pain. Patients with 
metastases to the base of the skull may complain of headache; pain on 
head movement; and face, neck, or shoulder pain (Greenberg, Deck, 
Vikram, et al., 1981). Besides pain and immobility, complications of 
bone metastases include fractures, hypercalcemia, and spinal cord 
compression. Pathologic fractures occur most commonly in cancers of 
the breast, lung, kidney, and thyroid and in multiple myeloma, usually 
in the proximal femur or humerus (Oda and Schurman, 1983). Hyper- 
calcemia is most often observed in cancers of the breast, lung, and 
kidney and in multiple myeloma. 

The diagnosis of bone metastasis is established by radiographic 
confirmation and, rarely, biopsy. Radionuclide scintigraphy and 
magnetic resonance imaging are the most sensitive means of detecting 
bone metastases, often demonstrating abnormalities before those seen 
on plain radiographs. Plain radiographs showing typical lytic, blastic, or 
mixed lesions are usually diagnostic and easily distinguished from 
lesions resulting from nonmetastatic causes (Wilner, 1982). However, 
plain radiographs and bone scintigraphy may be negative early in the 
course of myeloma, in some osseous metastases, and at sites of previ- 
ously radiated bone (Kelly and Payne, 1991). Magnetic resonance imag- 
ing may be helpful in such cases when bone involvement is suspected. 

Epidural Metastases/Spinal Cord Compression 



Epidural metastasis is the most ominous complication of bone 
metastasis to the vertebral spine and is a medical emergency. Failure 
to diagnose and treat this condition will lead to permanent neurologic 
deficits due to spinal cord dysfunction. Early diagnosis, before overt 
neurologic deficits, should result in improved outcome (Byrne, 1992). 
Epidural metastasis is a common complication in patients with breast, 
prostate, or lung cancer; multiple myeloma; renal cell carcinoma; or 

30 



Pain Assessment 

melanoma. The tumor enters the epidural space by contiguous spread 
from adjacent vertebral metastases in the vast majority of cases 
(Rodriguez and Dinapoli, 1980). The remaining cases arise from the 
direct invasion of retroperitoneal tumor or tumor located in the poste- 
rior thorax through adjacent intervertebral foramina or, rarely, from 
bloodborne seeding of the epidural space. The pain is usually midline, 
but patients whose tumor involves nerve roots have sharp or shooting 
pain in a radicular distribution. Untreated, the pain slowly intensifies 
with a mean duration of 7 weeks from the onset of pain to the onset of 
neurologic deficits due to spinal cord compression (Gilbert, Kim, and 
Posner, 1978). Signs of spinal cord compression include motor, 
sensory, and autonomic (e.g., bladder and bowel) dysfunction. 

More than 70 percent of patients with spinal cord compression have 
an abnormal plain radiograph in the region of pain (compression frac- 
ture, blastic, or lytic metastases) (Portenoy, Lipton, and Foley, 1987). 
Because pain is such a reliable early sign, epidural metastases can often 
be diagnosed and treated before neurologic deficits develop. Patients 
with persistent back pain in the region of abnormality on plain spine 
radiograph, with or without neurologic deficits, should undergo evalua- 
tion with MRI. Patients with progressive back or neck pain whose plain 
radiograph is normal should also undergo an imaging study of the 
epidural space, even if their neurologic examination is normal. Admin- 
istration of analgesics and corticosteroids constitutes the mainstay of 
pharmacologic therapy. Radiation therapy or surgical excision followed 
by radiation therapy are the two standard treatments. 

Metastases to the Skull 



Table 4 lists common metastases to the skull, which often cause pain 
in patients with cancer. 

Plexopathies 

Cervical, brachial, and lumbosacral plexi can be sources of 
intractable pain in cancer patients (Elliott and Foley, 1989). Pain is 
produced when these structures are infiltrated by tumor or compressed 
by fibrosis after radiation therapy to adjacent structures. Pain tends to 
be less prominent in radiation-induced plexopathies than in tumor- 
related ones. Traction injury related to the positioning of a patient 
during a prolonged operation may also produce brachial plexopathy. 

Pain originating in the cervical plexus often occurs as an aching 
discomfort that may radiate into the neck and occiput. It is most 
commonly caused by metastases to the cervical lymph nodes or the 
local extension of primary head and neck tumors. 

31 



Management of Cancer Pain 
Table 4. Metastases to the skull 



Type of 
metastases 



Signs and symptoms 



Middle fossa 
syndrome 



Jugular foramen 
syndrome 



Clivus metastases 



Orbital metastases 

Parasellar 
metastases 

Sphenoid sinus 
metastases 

Occipital condyle 
invasion 

Odontoid fractures 



Similar to trigeminal neuralgia, i.e., numbness, paresthesia, 
and pain referred to the second or third divisions of the fifth 
nerve, except that objective signs of neuropathy, e.g., corre- 
sponding sensory deficits and masseter weakness, may be 
present. Diplopia, dysarthria, headache, and dysphagia may 
develop as well. 

Occipital pain often radiating to the vertex and ipsilateral 
shoulder or neck; may be accompanied by local tenderness 
and exacerbation with movement of the head. Neurologic 
signs consistent with dysfunction of cranial nerves IX 
through XII and Horner's syndrome may be present. Lanci- 
nating throat pain (glossopharyngeal neuralgia) has been 
observed in association with the above symptoms or as the 
sole complaint. 

Vertex headache exacerbated by neck flexion; may be 
accompanied by either unilateral or bilateral cranial nerve 
dysfunction (IV through XXII). 

Retro-orbital or frontal headache often with diplopia, visual 
loss, proptosis, and extraocular nerve palsies. 

Symptoms similar to those of orbital metastases. 

Bifrontal headache radiating to both temples with 
intermittent retro-orbital pain. Nasal stuffiness, diplopia, and 
a unilateral or bilateral VI cranial nerve palsy may be present. 

Severe occipital pain that is exacerbated by movement and 
that may be accompanied by XII cranial nerve dysfunction. 

Usually caused by tumor or metastasis to atlas bone. Risk 
of spinal cord compression due to vertebral instability. 



Source: Adapted from Elliot and Foley, 1989; Greenberg, Deck, Vikram, et al., 1981 



Brachial plexopathy is a common complication of breast and lung 
cancer and lymphoma, but it can also be caused by metastasis to the 
brachial plexus from a remote primary tumor (Kori, Foley, and 
Posner, 1981). Pain occurs in up to 85 percent of patients with brachial 
plexus involvement and may precede weakness or sensory loss by 
months (Foley, 1987). When the upper plexus is damaged by tumor, 
pain usually begins in the shoulder and is associated with shooting or 
electrical sensations in the thumb and index finger. When the lower 
plexus is involved, as is more common, pain begins in the shoulder 
and radiates into the elbow, arm, and medial forearm, and into the 
fourth and fifth digits. In about 25 percent of patients, both upper and 



32 



Pain Assessment 

lower divisions are involved. Compared with tumor-related plexopa- 
thy, radiation damage to the brachial plexus causes less severe pain, 
distributed initially in the upper division. 

Epidural extension may occur in up to 50 percent of patients with 
superior pulmonary sulcus ("Pancoast") tumors (Kanner and Foley, 
1981). Epidural disease is more likely to occur when the entire plexus 
is involved and Horner's syndrome is present, which indicates medial 
and paraspinal spread of tumor. Lymphoma may produce brachial 
plexopathy and spinal cord compression in the absence of vertebral 
body erosion. CT and MRI of the brachial plexus and epidural spaces 
are the diagnostic procedures of choice, and are essential to define the 
extent of disease and to determine the appropriate radiation ports. 

The lumbosacral plexus, embedded in the psoas muscle, may be 
invaded by tumors of the abdomen and pelvis. Colorectal, endome- 
trial, and renal cancers, as well as sarcomas and lymphomas, may 
invade this plexus by direct spread. However, 25 percent of 
lumbosacral plexopathies are metastatic (Jaeckle, Young, and Foley, 
1985). Pain is usually felt in the lower abdomen, buttock, and leg. 
Infiltration of the sacral plexus may produce perineal and perirectal 
pain, which is exacerbated by sitting and lying prone. Pain typically 
precedes, by weeks or even months, the neurologic signs of weakness, 
sensory loss, or urinary incontinence. Abdominal and pelvic CT or 
MRI may provide the diagnosis and allow definition of radiation 
portals. Similar to patients with brachial plexopathy, patients with 
diffuse or bilateral lumbosacral plexus involvement may have an 
epidural extension of tumor, in which case, MRI of the epidural space 
is also required. Epidural disease of the cauda equina or 
leptomeningeal tumor may produce a clinical syndrome similar to 
lumbosacral plexopathy (Elliott and Foley, 1989). 

Pain may precede overt neurologic signs in spinal cord compres- 
sion, plexopathies, and spinal metastasis. Prompt recognition of these 
syndromes and institution of appropriate treatment can avoid paralysis 
and incontinence. 

Peripheral Neuropathies 



Peripheral nerves can be compressed or infiltrated by tumor or 
constricted by fibrosis, which in rare instances is a complication of 
radiation treatment. They may also be damaged by neurotoxic 
chemotherapy or by cutaneous incisions and the retraction of tissues 
during surgery (Table 5). 

Myeloma may cause a progressive painful neuropathy in about 15 
percent of patients. In as many as 8 of 10 such patients, neuropathy 
precedes the onset of other symptoms (Davis and Drachman, 1972). 
This sensorimotor neuropathy is characterized by distal paraesthesias, 

33 



Management of Cancer Pain 

Table 5. Common cancer pain syndromes due to 
peripheral nerve injury 



Pain syndrome 


Associated signs and symptoms 


Affected nerves 


Tumor infiltration of 
a peripheral nerve 


Constant, burning pain with 
dysesthesia in an area of sensory loss 

Pain is radicular and often unilateral 


Peripheral 


Postradical neck 
dissection 


Tight, burning sensation in 
the area of sensory loss 

Dysesthesias and shocklike pain may 
be present 

Second type of pain may occur mimicking 
a drooped shoulder syndrome 


Cervical plexus 


Postmastectomy 
pain 


Tight, constricting, burning pain in the 
posterior arm, axilla, and anterior 
chest wall 

Pain exacerbated by arm movement 


Intercostobrachial 


Postthoracotomy 
pain 


Aching sensation in the distribution of 
the incision with sensory loss with or 
without autonomic changes 

Often exquisite point tenderness at the 
most medial and apical points of the scar 
with a specific trigger point 

Secondary reflex sympathetic dystrophy 
may develop 


Intercostal 


Postnephrectomy 
pain 


Numbness, fullness, or heaviness in the 
flank, anterior abdomen, and groin 

Dysesthesias are common 


Superficial flank 


Postlimb 
amputation 


Phantom limb pain usually occurs after 
pain in the same site before amputation 

Stump pain occurs at the site of the 
surgical scar, several months to years 
after surgery. It is characterized by a 
burning dysesthetic sensation that is 
exacerbated by movement 


Peripheral endings 
and their central 
projections 



sensory loss, weakness, and muscle wasting, and it may occasionally 
ascend upward in a manner similar to Guillain-Barre syndrome. 

Vincristine, cisplatin, and taxol produce dose-related peripheral 
neuropathies, usually manifested as dysesthesia in the feet and later (as 
the neuropathy progresses) in the hands; continuous burning pain is 
rarely a problem. Vincristine neuropathy may also give rise to cranial 
neuralgias, including jaw claudication. Treatment of chemotherapy- 
related neuropathy involves decreasing or stopping the offending agent 
(when possible) and the use of analgesics. 



34 



Pain Assessment 



Pain syndrome 


Associated signs and symptoms 


Affected nerves 


Chemotherapy- 
induced 
peripheral 
neuropathy 


Painful paresthesias and dysesthesias 

Hyporeflexia 

Less frequently: motor and sensory loss; 
rarely: autonomic dysfunction 

Commonly associated with the vinca 
alkaloids, cisplatin, and Taxol 


Distal areas of 
peripheral (e.g., 
polyneuropathy) 


Radiation-induced 
peripheral nerve 
tumors 


May promote malignant fibrosarcoma 

Painful, enlarging mass in a previously 
irradiated area 

Patients with neurofibromatosis 
more susceptible 


Superficial and deep 


Cranial 
neuropathies 


Severe head pain with cranial 
nerve dysfunction 

Leptomeningeal disease 

Base of skull metastasis 


Cranial V, VII, IX, X, XI, 
XII are most common 


Acute and 

postherpetic 

neuropathy 


Painful paresthesia and dysesthesia 

Constant burning and aching pain 

Shocklike paroxysmal pain 

Immunosuppression from disease or 
treatment is a risk factor; postherpetic 
neuropathy incidence increases with age 


Thoracic and cranial 
(VI) are most common 



Note: See Chapters 3, 4, and 5 for treatment of cancer-related neuropathies. 
Source: Adapted from Foley, 1985b; Kanner, 1985; Payne 1985. 



In the absence of recurrent tumor, persistent pain following 
surgery may result from intraoperative injury to cutaneous or deeper 
nerves. Postsurgical pain syndromes are characterized by either persis- 
tent pain after the surgical procedure or recurrent pain after the initial 
surgical pain has resolved. The clinical characteristics relate to the 
location and extent of nerve injury (Kelly and Payne, 1991). Treat- 
ment of these syndromes involves the use of analgesics and, occasion- 
ally, regional nerve blocks. 



35 



Management of Cancer Pain 

Table 6. Common causes of abdominal pain 



Obstruction of small or large bowel. 

Occlusion of blood flow to visceral organs (e.g., liver, kidney, 

large and small bowel). 

Thrombosis and engorgement of splenic or renal veins. 

Omental metastasis. 

Volvulus of the small intestine. 

Infectious or chemical peritonitis. 

Metastasis or lymphomatous liver distention. 



Acute and Postherpetic Neuralgia. 



Varicella-zoster virus infection or reactivation ("shingles") is more 
likely to occur in patients with cancer than in the general population 
because of the higher incidence of immunosuppression in the former. 
Zoster neuralgia may cause acute and chronic pain (Rusthoven, 
Ahlgren, Elhakim, et al., 1988). Disseminated zoster is twice as likely 
to occur in patients with progressive tumor than those in remission 
(Rusthoven, Ahlgren, Elhakim, et al., 1988). Thoracic and cranial 
dermatomes are most commonly affected, and the incidence of 
postherpetic neuralgia (pain after healing of rash) increases with age 
(Watson, Evans, Reed, et al., 1982). 

Varicella-zoster virus infection is characterized by a burning, 
aching pain. Lancinating or shocklike pain may be superimposed in 
the area of the crusted (or healed) herpetic skin lesions, in which there 
is usually sensory loss. Hyperpathia may be profound. For acute 
zoster, antiviral therapies in combination with analgesics are recom- 
mended. For postherpetic neuralgia, antiviral therapies are of limited 
use, and therapies for neuropathic pain are used (see Chapter 3). 
Empiric observations suggest that nerve blocks during acute herpes 
zoster infection reduce pain, shorten the acute episode, and prevent 
the emergence of postherpetic neuralgia (Bonica, 1990). Treatment 
approaches for neuropathic pain are discussed later (see also Figure 1). 

Abdominal Pain 

Abdominal tumors are frequently characterized by pain that is 
colicky, worse after eating, and associated with nausea. Pain may be 
referred widely throughout the abdomen to distant cutaneous sites 
(e.g., shoulder, neck, and back). Patients with tumors of the small or 
large intestine occasionally have a combination of obstruction, pain, 

36 



Pain Assessment 
Table 7. Assessment of mucositis 

Examine lips and all mucosal surfaces for number, size, and location of lesions. 
Pain intensity is usually related to the degree of tissue damage. 

Include assessment of local edema and erythema as well as preexisting periodontal 
disease that may also be painful. 

Ask patient to identify painful or burning areas; even if there is no apparent tissue 
damage, these may become involved later. 

Culture suspicious lesions to rule out concomitant infection (bacterial, viral, fungal) 
that may intensify pain and delay healing. 

Evaluate patient's ability to swallow (including oral analgesics), and restrict oral 
intake if necessary. 

Repeat the assessment frequently because clinical signs and symptoms 
may change. 



and hematemesis or rectal bleeding. Common causes of abdominal 
pain for these patients are listed in Table 6. 

Patients with cancer are vulnerable to developing the same 
nonmalignant medical and surgical causes of abdominal pain, such as 
appendicitis, cholecystitis, and pancreatitis, as are individuals without 
cancer. Opioid analgesic therapy is often constrained in this group of 
patients by nausea, constipation, and ileus related to tumor-related 
bowel obstruction. Treatment of abdominal pain with nerve blocks is 
discussed in Chapter 5. 

Mucositis 

Mucositis can occur in any patient receiving cytotoxic chemother- 
apy or radiation to the head and neck. In patients receiving chemother- 
apy, the incidence and severity of mucosal toxicity is influenced by the 
individual drugs, their dosages, and the schedule of their administra- 
tion. Preexisting poor oral hygiene may also contribute to mucositis. 
Pain is often intense and interferes with oral intake. Chemotherapy- 
induced mucositis usually begins 3 to 5 days after therapy is started, 
reaches its peak at 7 to 10 days, and slowly resolves over the next 5 to 7 
days unless complicated by infection or hemorrhage (Dreizen, 1990). 
Clinical signs of mucositis include diminished mucosal thickness and 
keratinization, superficial sloughing, and ulceration. 

Radiation of the oropharyngeal and esophageal mucosa results in 
predictable inflammatory effects, usually appearing at the end of the 
second week of treatment, plateauing during the fourth week of radia- 
tion, and sometimes persisting for 2 to 3 weeks after the completion of 
treatment (Baker, 1982). Initially, the mucosa in the path of radiation 

37 



Management of Cancer Pain 

appears reddened and swollen; as treatment continues, the mucosa 
can be covered with a fibrous exudate. 

In both chemotherapy- and radiation-associated mucositis pain, 
intensity is related to the extent of tissue damage and the degree of 
local inflammation. Typically, the patient describes a burning sensa- 
tion, often accompanied by erythema. Because clinical signs and 
symptoms may change, patients with mucositis should be assessed 
frequently (Table 7). Management involves the aggressive use of anal- 
gesics (such as systemic patient-controlled analgesia) and agent- 
specific antimicrobial agents (Epstein, 1990; Janjan, Weissman, and 
Pahule, 1992). 

Assessment of New Pain 

Pain assessment is an ongoing process requiring constant attention 
to new pain (see Figure 1). Changes in pain patterns or the develop- 
ment of new pain should not be attributed to preexisting causes but 
should instead trigger diagnostic evaluation. New pain may signal 
treatable problems such as infection or fracture. A change in pain 
often signals advancing disease, and because pain management relies 
on the treatment of the underlying disease, establishing a medical 
diagnosis with the criteria discussed earlier is critical. A 1992 report 
showed that a comprehensive pain assessment revealed new causes of 
pain in 64 percent of 270 oncology patients with new pain complaints; 
most of the new diagnoses were neurologic (Gonzales, Payne, Foley, 
et al., 1992). Thus, the need to reassess persistent pain to identify new 
causes cannot be overemphasized. 



38 



3 



Pharmacologic Management 

Recommendations 

13. An essential principle in using medications to manage cancer pain 
is to individualize the regimen to the patient. (A) 

14. The simplest dosage schedules and least invasive pain manage- 
ment modalities should be used first. (Panel Consensus) 

15. Pharmacologic management of mild to moderate cancer pain 
should include an NS AID or acetaminophen, unless there is a 
contraindication. (A) 

16. When pain persists or increases, an opioid should be added. (A) 

17. Treatment of persistent or moderate to severe pain should be 
based on increasing the opioid potency or dose. (A) 

18. Medications for persistent cancer-related pain should be 
administered on an around-the-clock basis with additional "as- 
needed" doses, because regularly scheduled dosing maintains a 
constant level of drug in the body and helps to prevent a recur- 
rence of pain. (A) 

19. Patients receiving opioid agonists should not be given a mixed 
agonist-antagonist because doing so may precipitate a withdrawal 
syndrome and increase pain. (B) 

20. Meperidine should not be used if continued opioid use is 
anticipated. (B) 

21. Opioid tolerance and physical dependence are expected with long- 
term opioid treatment and should not be confused with addiction. 
(Panel Consensus) 

22. The oral route is the preferred route of analgesic administration 
because it is the most convenient and cost-effective method of 
administration. When patients cannot take medications orally, 
rectal and transdermal routes should be considered because they 
are also relatively noninvasive. (Panel Consensus) 

23. Intramuscular administration of drugs should be avoided because 
this route can be painful and inconvenient, and absorption is not 
reliable. (B) 

24. Failure of maximal systemic doses of opioids and coanalgesics 
should precede the consideration of intraspinal analgesic systems. 
(Panel Consensus) 

39 



Management of Cancer Pain 

25. Because there is great interindividual variation in susceptibility to 
opioid-induced side effects, clinicians should monitor for these 
potential side effects. (B) 

26. Constipation is a common problem associated with long-term 
opioid administration and should be anticipated, treated prophy- 
lactically, and monitored constantly. (B) 

27. Naloxone, when indicated for reversal of opioid-induced respira- 
tory depression, should be titrated in doses that improve respira- 
tory function but do not reverse analgesia. (B) 

28. Placebos should not be used in the management of cancer pain. 
(Panel Consensus) 

29. Patients should be given a written pain management plan. (A) 

30. Communication about pain management should occur when a 
patient is transferred from one setting to another. (B) 

Drug therapy is the cornerstone of the many modalities available 
to manage cancer pain because it is effective, relatively low risk, inex- 
pensive, and usually of rapid onset. An essential principle in using 
medications to manage cancer pain is to individualize the regimen to 
the patient (Foley, 1985a). 

Three major classes of drugs are used alone or, more commonly, in 
combination to manage pain in the cancer patient: 

■ NSAIDs and acetaminophen (APAP). 

■ Opioid analgesics. 

■ Adjuvant analgesics. 

Before choosing drugs to manage pain or other symptoms, identify 
the specific cause(s) of the pain, evaluate its intensity and quality, and 
then match the drug to the pain intensity and other characteristics. 
The simplest dosage schedules and least invasive pain management 
modalities should be used first. After drug therapy has been started, 
pain should be assessed to determine the ongoing effectiveness of the 
analgesic therapy. For opioid analgesics, if pain relief is inadequate, 
the dose should be increased until pain relief is achieved or unaccept- 
able side effects occur. In the case of NSAIDs and adjuvant analgesic 
drugs, which have ceiling effects to their analgesic efficacy, if the 
upper limit of the recommended dose is reached and pain relief is not 
achieved, then that particular drug should be discontinued and a 
second drug in that class should be used. 

Most cancer pain can be managed by oral administration of drugs; 
however, difficulty in swallowing, gastrointestinal (GI) disturbances 
that render drug absorption unreliable, the amount of drug required, 

40 



Pharmacologic Management 

and many other factors may require alternative routes of administra- 
tion (Coyle, Adelhardt, Foley, et al., 1990; Grond, Zech, Schug, et al., 
1991). Table 8 summarizes some of the advantages and disadvantages 
of cancer pain therapies. 

The WHO Ladder 

A simple, well- validated, and effective method for assuring the 
rational titration of therapy for cancer pain has been devised by WHO 
(World Health Organization, 1990). It has been shown to be effective 
in relieving pain for approximately 90 percent of patients with cancer 
(Ventafridda, Caraceni, and Gamba, 1990) and over 75 percent of 
cancer patients who are terminally ill (Grond, Zech, Schug, et al., 
1991). This approach is based on the concept of an analgesic ladder 
(Figure 2). 

The five essential concepts in the WHO approach to drug therapy 
of cancer pain are: 

■ By the mouth. 

■ By the clock. 

■ By the ladder. 

■ For the individual. 

■ With attention to detail. 

The first step in this approach is the use of acetaminophen, aspirin, 
or another NSAID for mild to moderate pain. Adjuvant drugs to 
enhance analgesic efficacy, treat concurrent symptoms that exacerbate 
pain, and provide independent analgesic activity for specific types of 
pain may be used at any step. 

When pain persists or increases, an opioid such as codeine or 
hydrocodone should be added (not substituted) to the NSAID. 
Opioids at this step are often administered in fixed dose combinations 
with acetaminophen or aspirin because this combination provides 
additive analgesia (Weingart, Sorkness, and Earhart, 1985). Fixed- 
combination products may be limited by the content of aceta- 
minophen or NSAID, which may produce dose-related toxicity. When 
higher doses of opioid are necessary, the third step is used. At this step 
separate dosage forms of the opioid and nonopioid analgesic should 
be used to avoid exceeding maximally recommended doses of aceta- 
minophen or NSAID. 

Pain that is persistent, or moderate to severe at the outset, should 
be treated by increasing opioid potency or using higher dosages. 

continued on page 45 

41 



Table 8. Advantages and disadvantages of pain therapies 



Intervention 


Advantages 


Disadvantages 


Oral analgesics 

Acetaminophen 

Aspirin 

NSAIDs 


1 . Useful for a wide variety of mild 
to moderate pains. 

2. Widely available, some over the 
counter. 

3. Additive analgesia when combined 
with opioids and other modalities. 

4. Can be administered by patient 
or family. 

5. Some are inexpensive. 


1 . Ceiling effect to analgesia. 

2. Side effects, especially 
gastritis and renal toxicity, can 
be serious. 

3. May risk bleeding in severely 
thrombocytopenic patients. 

4. Only one NSAID (ketorolac) 

is available now for parenteral 
administration. 

5. Many are expensive. 


Oral opioids 


1 . Effective for both localized and 
generalized pain. 

2. Ceiling to analgesic effectiveness 
imposed only by side effects. 

3. Multiple drug choices in this class. 

4. Sedative and anxiolytic properties 
useful in some acute treatment 
settings. 

5. Can be administered by patient 
or family. 

6. Some are inexpensive. 

7. Long acting, controlled-release 
forms available. 


1 . Side effects may limit 
analgesic effectiveness. 

2. Prescription of these 
substances is regulated. 

3. Stigma or fears associated 
with use. 


Transdermal 

opioids 

(fentanyl) 


1 . Long duration of action (48-72 
hours) from single patch. 

2. Allows use of a strong opioid 
(fentanyl) in outpatient settings for 
some patients who have not 
tolerated morphine and related 
drugs. 

3. Many patients find them easy to use. 

4. Provides continuous administration 
of an opioid without use of needles 
or pumps. 

5. Can be administered by patient 
or family. 


1 . Side effects may not be as 
quickly reversible as in oral 
opioid administration. 

2. Difficult to modify dosage 
rapidly. 

3. Relatively slow onset of action. 

4. Requires additional 
short-acting medicine 
for breakthrough pain. 

5. Expensive. 


Rectal opioids 


1 . Relatively easy-to-use alternative 
route when the oral route is 
unavailable. 

2. Other opioid suppositories 
available for morphine-intolerant 
patients. 

3. Can be administered by patient 
or family. 

4. Less expensive than subcutaneous 
or intravenous infusions. 


1 . Not widely accepted by 
patients or families. 

2. Side effects may limit 
analgesic effectiveness. 

3. Relatively slow onset of action. 

4. Contraindicated if low white 
blood cell or platelet counts 
(risks of infection, bleeding). 


Subcutaneous 
infusion 


1 . Can provide rapid pain relief 
without intravenous access. 

2. Morphine or hydromorphone are 
the preferred drugs for this route 
when administered in the home. 

3. When used in PCA mode, allows 
for rapid individual dose titration 
and provides sense of control for 
patient. 


1 . Only a limited volume of 
infusate can be administered 
(e.g., 2 to 4 ml/hour). 

2. Induration, irritation at infusion 
site may be a complication. 

3. Requires skilled nursing and 
pharmacy support. 

4. Often requires expensive drug 
infusion pump and recurring 
charges for disposables. 



42 



Pharmacologic Management 



Intervention 


Advantages 


Disadvantages 


Intravenous 
infusion 


1 . Can provide rapid pain relief. 

2. Almost all opioids can be given 
by this route. 

3. Not limited by infusate volumes. 

4. When used in PCA mode, allows 
for rapid individual dose titration 
and provides sense of control 
for patient. 


1 . Infection and infiltration of 
intravenous lines are potential 
complications. 

2. Requires skilled nursing and 
pharmacy support. 

3. Often requires expensive drug 
infusion pump and recurring 
charges for disposables. 


Epidural, 
intrathecal, and 
intracerebral 
ventricular 
routes 


1 . Useful for pain that has not 
responded to less invasive 
measures. 

2. Local anesthetics may be added to 
spinal opioids and may produce 
additive analgesia. 


1 . Tolerance may occur sooner 
than with oral or rectal 
administration. 

2. Infection at catheter site can 
produce meningitis and/or 
epidural abscess. 

3. Pruritus and urinary retention 
are more common than with 
oral or parenteral opioid 
administration. 

4. Contraindicated in presence of 
acute spinal cord compression. 

5. Requires special expertise. 

6. Requires careful monitoring, 
especially when therapy 
begins and when doses are 
increased. 

7. May require expensive drug 
infusion pump, intervention 
fees, and recurring charges 
for disposables. 


Regional 

neurolytic 

blocks 


1 . Effective for pain relief with certain 
diagnoses (e.g., pancreatic cancer). 

2. May be useful for movement-related 
and abdominal visceral pain that is 
refractory to drug therapy. 

3. Can allow dosage (and side effect) 
reduction of systemic drugs for 
localized pain. 


1 . Risk of postural hypotension, 
bowel and bladder incontinence, 
and leg weakness. 

2. Procedure is irreversible. 

3. Requires special expertise. 

4. Expenses for specialized care 
and operating room costs. 


Ablative 
neurosurgery 


1 . May be useful for movement-related 
lower body pain that is refractory 

to drug therapy. 

2. Fast onset of pain relief. 

3. Percutaneous cordotomy can be 
done under local anesthesia. 

4. Can allow dosage (and side effect) 
reduction of systemic drugs for 
localized pain. 


1 . Six-month duration of pain 
relief for cordotomy is 
only 50%. 

2. Procedure is irreversible. 

3. Requires special expertise. 

4. Expensive because of 
specialized care and operating 
room costs. 



43 



Table 8. Advantages and disadvantages of pain therapies, continued 



Intervention 


Advantages 


Disadvantages 


Corticosteroids 


1 . Effective in pain associated with 
inflammatory component 
(e.g., bone pain). 

2. Can produce cytotoxic effect 
against some tumors. 

3. May be given orally or intravenously. 

4. May increase appetite. 

5. May produce euphoria in some 
patients. 

6. May decrease pain associated with 
CNS and spinal cord tumors. 


1 . Prolonged use associated 
with adrenal suppression, 
fluid and electrolyte 
disturbance. 

2. Increases risk of gastritis. 

3. Prolonged use may decrease 
cell-mediated immunity and 
increase risk of infection. 

4. Some patients experience 
emotional instability or 
psychoses. 

5. May suppress (mask) fevers 
associated with infections. 


Anticonvulsants 


1 . Useful for peripheral pain 
syndromes associated with 
neuropathic pain, especially 
lancinating or shooting pain. 


1. May increase sedation. 

2. Monitoring required to avoid 
specific toxicities associated 
with increased serum levels. 

3. Idiosyncratic or dose-related 
bone marrow suppression may 
limit usefulness. 


Antidepressants 


1 . Useful in pain syndromes 
associated with neuropathic pain 
and with pain caused by surgery, 
chemotherapy, or nerve infiltration. 

2. May promote sleep when taken at 
bedtime. 


1 . May increase sedation. 

2. Anticholinergic side effects 
of many antidepressants 
are distressing to many 
patients. 

3. CNS, cardiovascular, and 
hepatic toxicities may limit 
usefulness. 


Hydroxyzine 


1 . When given in high dosages 

(100 mg),some antihistamines may 
produce additive analgesia with 
therapeutic doses of opioids. 

2. May be beneficial in patients with 
opioid-induced nausea and 
vomiting. 


1 . In high doses demonstrates 
a significant potential for 
causing respiratory depression 
which is additive to that of 
opioids, but not reversible 
with naloxone. 

2. Can cause significant 
sedation. 


Radiation 
therapy 


1 . Directly treats tumor, especially 
useful for bone metastasis. 

2. Can provide fast onset of pain relief. 

3. Single dose is effective for some 
patients. 

4. Widely available mode of treatment. 

5. Radiopharmaceuticals and some 
forms of radiation therapy can treat 
multiple disease sites. 


1 . When multiple fractions are 
given, it may entail 
prolonged inconvenience 
and discomfort for patients. 

2. Myelosuppression may 
occur, especially with prior 
chemotherapy when wide 
teletherapy or radiopharma- 
ceuticals are used. 


Relaxation, 
imagery, 
biofeedback, 
distraction, and 
reframing 


1 . May decrease pain and anxiety 
without drug-related side effects. 

2. Can be used as adjuvant therapy 
with most other modalities. 

3. Can increase patient's sense 
of control. 

4. Most are inexpensive, require no 
special equipment, and are easily 
administered. 


1 . Patient must be motivated to 
use self-management 
strategies. 

2. Requires professional time to 
teach interventions. 



44 



Pharmacologic Management 



Intervention 


Advantages 


Disadvantages 


Patient 


1. 


Effective in improving ability to 


1 . Requires professional time to 


education 




follow medical regimen and in 


teach pain management 






decreasing pain. 


regimens. 




2. 


Multiple teaching aids available. 






3. 


Promotes self-care in pain 
treatment and management of 
side effects. 




Psychotherapy, 


1. 


May decrease pain and anxiety 


1 . Requires skilled therapist. 


structured 




for patients who have pain that is 




support, and 




difficult to manage. 




hypnosis 


2. 


May increase patient's coping skills. 




Cutaneous 


1. 


May reduce pain, inflammation, 


1 . Heat may increase bleeding 


stimulation 




and/or muscle spasm. 


and edema after acute injury. 


(superficial 


2. 


Can be used as adjuvant therapy 


2. Cold is contraindicated for 


heat, cold, and 




with most other modalities. 


use over ischemic tissues. 


massage) 


3. 


Relatively easy to use. 






4. 


Can be administered by patients 
or families. 






5. 


Relatively low cost. 




Transcutaneous 


1. 


May provide pain relief without 


1 . Requires skilled therapist to 


electrical nerve 




drug-related side effects. 


initiate therapy. 


stimulation 


2. 


Can be used as adjuvant therapy 


2. Potential risk of infection, 






with most other modalities. 


bleeding. 




3. 


Gives patient sense of control 
over pain. 




Acupuncture 


1. 


May provide pain relief without 
side effects. 


1 . Requires skilled therapist. 




2. 


Can be used as adjuvant with most 
other therapies. 




Peer support 


1. 


May increase patient's coping skills. 


1 . None identified. 


groups 


2. 


Increases sense of control. 






3. 


Provides support for families 
and patients. 




Pastoral 


1. 


May increase patient's coping skills. 


1 . None identified. 


counseling 


2. 


May provide spiritual and 
emotional comfort. 





Drugs such as codeine or hydrocodone are replaced with more potent 
opioids (usually morphine, hydromorphone, methadone, fentanyl, or 
levorphanol), as described below. 

Medications for persistent cancer-related pain should be adminis- 
tered on an around-the-clock basis, with additional "as-needed" 
doses, because regularly scheduled dosing maintains a constant level 
of drug in the body and helps to prevent a recurrence of pain. Patients 
who have moderate to severe pain when first seen by the clinician 
should be started at the second or third step of the ladder. 



45 



Management of Cancer Pain 

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 

NSAIDs are used as initial therapy in mild pain because they are 
effective, are often available over the counter, and can be used effec- 
tively in combination with opioids and adjuvant analgesics if pain 
intensity increases. Acetaminophen is included with this group, even 
though its anti-inflammatory effects are less potent, because it has 
similar analgesic potency and pharmacologic characteristics. A major 
advantage of acetaminophen in comparison to other NSAIDs is its 
lack of effect on platelet function, which makes it less risky to use in 
thrombocytopenic patients. It is also relatively inexpensive. 

NSAIDs decrease levels of inflammatory mediators generated at 
the site of tissue injury by inhibiting the enzyme cyclooxygenase, 
which catalyzes the conversion of arachidonic acid to prostaglandins 
and leukotrienes (Sunshine and Olson, 1989). These mediators sensi- 
tize nerves to painful stimuli. Although NSAIDs may also affect the 
central nervous system, these drugs do not activate opioid receptors 
and therefore produce analgesia by a different mechanism than 
opioids. Hence: 

■ The concurrent use of opioids, NSAIDs, and acetaminophen often 
provides more analgesia than does either of the drug classes alone. 

■ The addition of NSAIDs and acetaminophen to opioid analgesics 
may achieve a "dose-sparing" effect such that lower doses of 
opioids may now produce pain relief with fewer side effects 
(Hodsman, Burns, Blyth, et al., 1987; Weingart, Sorkness, and 
Earhart, 1985). 

In contrast to opioids, NSAIDs do not produce tolerance, physical, 
or psychological dependence, are antipyretic, and have a different 
spectrum of toxicity. Used as single agents, NSAIDs have a ceiling 
effect on their analgesic potential, so the use of doses higher than 
those specified in the package insert is not recommended. 

The nonacetylated salicylates such as salsalate, sodium salicylate, 
and choline magnesium trisalicylate do not affect platelet aggregation 
profoundly and do not alter bleeding time (Danesh, Saniabadi, 
Russell, et al., 1987; Day, Furst, Graham, et al., 1987; Estes and 
Kaplan, 1980; Morris, Sherman, McQuain, et al., 1985; Stuart and 
Pisko, 1981; Zucker and Rothwell, 1978). Aspirin, the prototype of the 
acetylated salicylate, produces an irreversible inhibition of platelet 
aggregation, which may prolong bleeding time for up to several days 
after ingestion (Stuart, Murphy, Oski, et al., 1972; Sutor, Bowie, and 
Owen, 1971; Weiss, Aledont, and Kochwa, 1968). The nonacetylated 
salicylates, such as sodium salicylate and choline magnesium trisalicy- 
late, have minimal effects on platelet aggregation and do not appear 

46 



Pharmacologic Management 

to alter bleeding time clinically (Day, Furst, Graham, et al., 1987; 
Morris, Sherman, McQuain, et al., 1985; Stuart and Pisko, 1981; 
Zucker and Rothwell, 1978). Other NSAIDs produce a reversible 
inhibition of platelet aggregation, which persists while the drug is in 
the systemic circulation (Schlegel, 1987). Therefore, with the excep- 
tion of the nonacetylated salicylates noted above, NSAIDs should be 
avoided if possible in patients who are thrombocytopenic or who have 
a clotting impairment. 

NSAIDs bind extensively to plasma proteins and therefore may be 
displaced by or may displace other protein-bound drugs such as 
Coumadin, methotrexate, digoxin, cyclosporine, oral antidiabetic 
agents, and sulfa drugs. Such interactions may enhance therapeutic or 
toxic effects of either drug. The use of NSAIDs has been associated 
with both minor (dyspepsia, heartburn, nausea, vomiting, anorexia, 
diarrhea, constipation, flatulence, bloating, epigastric pain, and 
abdominal pain) and major (bleeding, ulceration, and perforation) GI 
toxicities. Serious effects are not always preceded by minor GI effects; 
patients should be advised to report any GI disturbances. 

Hepatic and renal dysfunction or toxicity, which can occur at any 
time in the course of NSAID therapy, are of particular concern during 
long-term use (Sunshine and Olson, 1989). The risk of renal dysfunc- 
tion is greatest in patients with advanced age, preexisting renal impair- 
ment, heart failure, hepatic dysfunction, hypovolemia, concomitant 
therapy with other nephrotoxic drugs such as diuretics, or elevated 
levels of angiotensin II or catecholamines. Antipyretic and anti- 
inflammatory effects of NSAIDs may mask the usual signs and symp- 
toms of infections. 

Adverse effects of NSAIDs that may appear at any time include: 

■ Renal failure. 

■ Hepatic dysfunction. 

■ Bleeding. 

■ Gastric ulceration. 

Even though NSAIDs are effective in relieving mild pain and are 
opioid sparing for moderate to severe pain, patients who take them, 
especially if elderly, should be monitored carefully for adverse effects. 

Most NSAIDs are available as oral tablets, caplets, or capsules, 
and several are available as oral liquids. Rectal suppositories of 
aspirin, acetaminophen, and other NSAIDs are commercially avail- 
able or can be compounded easily by pharmacists. Ketorolac 
tromethamine is the only NSAID that is currently available for short- 
term parenteral administration. Table 9 provides dosing data for 
acetaminophen and NSAIDs. 

47 



Table 9. Dosing data for acetaminophen (APAP) and NSAIDs 



Drug 


Usual dose for adults 

and children 
5* 50 kg body weight 


Usual dose for children 1 

and adults 2 

ss 50 kg body weight 


Acetaminophen and over-the-counter NSAIDs 


Acetaminophen 3 


650 mg q 4 h 
975 mg q 6 h 


10-15 mg/kgq4h 
15-20 mg/kg q 4 h (rectal) 


Aspirin 4 


650 mg q 4 h 
975 mg q 6 h 


10-15 mg/kgq4h 

1 5-20 mg/kg q 4 h (rectal) 


Ibuprofen (Motrin, 
others) 


400-600 mg q 6 h 


1 mg/kg q 6-8 h 5 


Prescription NSAIDs 


Carprofen (Rimadyl) 


1 00 mg tid 




Choline magnesium 
trisalicylate 6 (Trilisate) 


1 ,000-1 ,500 mg tid 


25 mg/kg tid 


Choline salicylate 
(Arthropan) 6 


870 mg q 3-4 h 




Diflunisal (Dolobid) 7 


500 mgq 12 h 




Etodolac (Lodine) 


200-400 mg q 6-8 h 




Fenoprofen calcium 
(Nalfon) 


300-600 mg q 6 h 




Ketoprofen (Orudis) 


25-60 mg q 6-8 h 




Ketorolac 
tromethamine 8 
(Toradol) 


10 mg q 4-6 h to a maximum 
of 40 mg/day 




Magnesium salicylate 
(Doan's, Magan, 
Mobidin, others) 


650 mg q 4 h 




Meclofenamate sodium 
(Meclomen) 9 


50-100mgq6h 




Mefenamic acid 
(Ponstel) 


250 mg q 6 h 




Naproxen (Naprosyn) 


250-275 mg q 6-8 h 


5 mg/kg q 8 h 


Naproxen sodium 
(Anaprox) 


275 mg q 6-8 h 




Sodium salicylate 
(Generic) 


325-650 mg q 3-4 h 




Parenteral NSAIDs 


Ketorolac 
tromethamine 8 - 10 
(Toradol) 


60 mg initially, then 30 mg 
q 6 h Intramuscular dose 
not to exceed 5 days 





48 



Pharmacologic Management 

It is impossible to predict which NSAID will be best tolerated by a 
particular patient; no particular NSAID has demonstrated superiority 
over others for pain relief. Once an NSAID has been selected, the 
dose should be increased until pain has been relieved or the maximal 
recommended dose has been achieved. The duration of analgesia does 
not always correlate with the serum half-life of the NSAID. There- 
fore, the response of the patient should guide the clinician in selecting 
dosing- intervals of these agents. Because NSAIDs and adjuvant anal- 
gesics have ceiling effects to their efficacy, if a patient does not 
respond to the maximal dose of one NSAID, another should be tried 
before discontinuation of NSAID therapy. The initial choice of 
NSAID should be based on the efficacy, safety, and relative expense; 
generally, the least expensive NSAID should be chosen. 

Opioids 

Opioids are the major class of analgesics used in the management 
of moderate to severe pain because of their effectiveness, ease of titra- 
tion, and favorable risk-to-benefit ratio. Opioids produce analgesia by 
binding to specific receptors both within and outside the CNS (Stein, 
1993; Hargreaves and Joris, 1993). Opioid analgesics are classified as 
full agonists, partial agonists, or mixed agonist-antagonists, depending 
on the specific receptors to which they bind and their intrinsic activity 
at that receptor. 

Commonly used full agonists include morphine, hydromorphone, 
codeine, oxycodone, hydrocodone, methadone, levorphanol, and 
fentanyl. These opioids are classified as full agonists because they do 
not have a ceiling to their analgesic efficacy and will not reverse or 



1 Only drugs that are FDA approved as an analgesic for use in children are included. 

2 Acetaminophen and NSAID dosages for adults weighing less than 50 kg should be adjusted 

for weight. 

3 APAP lacks the peripheral anti-inflammatory and antiplatelet activities of the other NSAIDs. 

4 The standard against which other NSAIDs are compared. May inhibit platelet aggregation for 

5=1 week and may cause bleeding. Aspirin is contraindicated in children with fever or other 

viral disease because of its association with Reye's syndrome. 

5 Not FDA approved for use in children as an over-the-counter drug; has FDA approval for use 

in children as a prescription drug for fever. However, clinicians have experience in prescribing 

ibuprofen for pain in children. 

6 May have minimal antiplatelet activity. 

Administration with antacids may decrease absorption. 

8 For short-term use only. 

9 Coombs-positive autoimmune hemolytic anemia has been associated with prolonged use. 

10 Has the same Gl toxicities as oral NSAIDs. 

Note: Only the above NSAIDs have FDA approval for use as simple analgesics, but clinical 
experience has been gained with other drugs as well. 

49 



Management of Cancer Pain 

antagonize the effects of other opioids within this class given simulta- 
neously. Side effects include constipation, nausea, urinary retention, 
confusion, sedation, and respiratory depression. 

Buprenorphine is a partial agonist. It has a relatively low intrinsic 
efficacy at the opioid receptor in comparison to full opioid agonists 
and displays a ceiling effect to analgesia. 

Mixed agonist-antagonists in clinical use include pentazocine, 
butorphanol tartrate, dezocine, and nalbuphine hydrochloride. These 
drugs have an analgesic ceiling. In contrast to full agonists, these drugs 
block opioid analgesia at one type of opioid receptor (mu) or are 
neutral at this receptor while simultaneously activating a different 
opioid receptor (kappa). Patients receiving full opioid agonists should 
not be given a mixed agonist-antagonist because doing so may precipi- 
tate a withdrawal syndrome and increase pain. 

Morphine is the most commonly used opioid for moderate to 
severe pain because of its availability in a wide variety of dosage 
forms, its well-characterized pharmacokinetics and pharmacodynam- 
ics, and its relatively low cost. 

Meperidine may be useful for brief courses (e.g., a few days) to 
treat acute pain and to manage rigors (shivering) induced by medica- 
tion, but it generally should be avoided in patients with cancer 
because of its short duration of action (2.5 to 3.5 hours) and its toxic 
metabolite, normeperidine. This metabolite accumulates, particularly 
when renal function is impaired, and causes CNS stimulation, which 
may lead to dysphoria, agitation, and seizures (Kaiko, Foley, Grabin- 
ski, et al., 1983). Therefore, meperidine should not be used if contin- 
ued opioid use is anticipated. 

Equianalgesic doses of commonly used opioids and starting doses 
for those drugs are listed in Tables 10 and 11. 

Tolerance and Physical Dependence 



Opioid tolerance and physical dependence are expected with long- 
term opioid treatment and should not be confused with psychological 
dependence ("addiction")? manifested as drug abuse behavior. The 

misunderstanding of these terms in relation to opioid use leads to inef- 
fective practices in prescribing, administering, and dispensing opioids 
for cancer pain and contributes to the problem of undertreatment. 

The presence of opioid tolerance and physical dependence does 
not equate with "addiction." 

Physical dependence on opioids is revealed when the opioid is 
abruptly discontinued or when naloxone is administered and is typi- 
cally manifested as anxiety, irritability, chills and hot flashes, joint 
pain, lacrimation, rhinorrhea, diaphoresis, nausea, vomiting, and 
abdominal cramps and diarrhea. The mildest form of the opioid 

50 



Pharmacologic Management 

abstinence syndrome may be confused with viral "flu-like" syndromes. 
For opioids with short half-lives (i.e., codeine, hydrocodone, 
morphine, hydromorphone), the onset of withdrawal symptoms can 
occur within 6 to 12 hours and peak at 24 to 72 hours after discontinu- 
ation. For opioids with long half-lives (i.e., methadone, levorphanol, 
transdermal fentanyl), the onset of the abstinence syndrome may be 
delayed for 24 hours or more after drug discontinuation and may be of 
milder intensity. The appearance of the abstinence syndrome defines 
physical dependence on opioids, which may occur after just 2 weeks of 
opioid therapy, but does not imply psychological dependence or addic- 
tion. Most patients with cancer take opioids for more than 2 weeks, 
and only very rarely do they exhibit the drug abuse behaviors and 
psychological dependence that characterize addiction (Portenoy and 
Payne, 1992). 

Patients with cancer occasionally require discontinuation or rapid 
decreases in doses of opioids when the cause of pain is effectively 
eliminated by antineoplastic treatments or pain perception is modified 
by neuroablative or neurolytic procedures. In such circumstances, the 
opioid abstinence syndrome can be avoided by withdrawal of the 
opioid on a schedule that provides half the prior daily dose for each of 
the first 2 days and then reduces the daily dose by 25 percent every 
2 days thereafter until the total dose (in morphine equivalents) is 
30 mg/day. The drug may be discontinued after 2 days on the 30 mg/day 
dose (American Pain Society, 1992). Transdermal clonidine (0.1 to 
0.2 mg/day) may reduce anxiety, tachycardia, and other autonomic 
symptoms associated with opioid withdrawal. 

Tolerance to opioids is defined as the need to increase dose 
requirements over time to maintain pain relief. For most cancer 
patients, the first indication of tolerance is a decrease in the duration 
of analgesia for a given dose. Increasing dose requirements are most 
consistently correlated with progressive disease, which produces 
increased pain intensity (Foley, 1985a). Patients with stable disease do 
not usually require increasing doses (Foley, 1993; Levy, 1989). 

Dosage Titration 

Opioid doses should be adjusted in each patient to achieve pain 
relief with an acceptable level of adverse effects. Dosage typically 
requires adjustment over time. With the exception of fentanyl deliv- 
ered by the transdermal route, there is no ceiling or maximal recom- 
mended dose for full opioid agonists, and in fact, very large doses of 
morphine, e.g., several hundred milligrams every 4 hours, may be 
needed for severe pain (Foley, 1985a). 

Effective pain relief can be accomplished by the anticipation and 
prevention of pain. Because many patients have persistent or daily 



51 



Table 10. Dose equivalents for opioid analgesics in opioid-naive 
adults and children ^50 kg body weight 1 



Drug 


Approximate 
equianalgesic dose 


Usual starting dose 

for moderate to 

severe pain 




Oral 


Parenteral 


Oral 


Parenteral 


Opioid agonist 2 


Morphine 3 


30 mg q 3-4 h 
(repeat around- 
the-clock 
dosing) 

60 mg q 3-4 h 
(single dose or 
intermittent 
dosing) 


1 mg q 3-4 h 


30 mg q 3-4 h 


10mgq3-4h 


Morphine, 
controlled-release 34 
(MS Contin, 
Oramorph) 


90-1 20 mg 
q12h 


N/A 


90-120 mg 
q12h 


N/A 


Hydromorphone 3 
(Dilaudid) 


7.5 mg q 3-4 h 


1 .5 mg q 3-4 h 


6 mg q 3-4 h 


1 .5 mg q 3-4 h 


Levorphanol 
(Levo-Dromoran) 


4 mg q 6-8 h 


2 mg q 6-8 h 


4 mg q 6-8 h 


2 mg q 6-8 h 


Meperidine 
(Demerol) 


300 mg 
q2-3h 


100mgq3h 


N/R 


100mgq3h 


Methadone 
(Dolophine, other) 


20 mg q 6-8 h 


10mgq6-8h 


20 mg q 6-8 h 


1 mg q 6-8 h 


Oxymorphone 3 
(Numorphan) 


N/A 


1 mg q 3-4 h 


N/A 


1 mg q 3-4 h 


Combination opioid/NSAID preparations 5 


Codeine 6 (with 
aspirin or 
acetaminophen) 


1 80-200 mg 
q3-4h 


130 mg 

q3-4h 


60 mg q 3-4 h 


60 mg q 2 h 
(IM/SC) 


Hydrocodone (in 
Lorcet, Lortab, 
Vicodin, others) 


30 mg q 3-4 h 


N/A 


10mgq3-4h 


N/A 


Oxycodone 

(Roxicodone, also in 
Percocet, Percodan, 
Tylox, others) 


30 mg q 3-4 h 


N/A 


10mgq3-4h 


N/A 



1 Caution: Recommended doses do not apply for adult patients with body weight less than 50 
kg. For recommended starting doses for children and adults < 50 kg body weight, see Table 1 1 . 
2 Caution: Recommended doses do not apply to patients with renal or hepatic insufficiency or 
other conditions affecting drug metabolism and kinetics. 

3 Caution: For morphine, hydromorphone, and oxymorphone, rectal administration is an alter- 
nate route for patients unable to take oral medications. Equianalgesic doses may differ from 



52 



Pharmacologic Management 

pain, it is important to use opioids on a regular schedule rather than 
only "as needed." Around-the-clock administration of analgesics 
allows each dose to become effective before the previous dose has lost 
its effectiveness. A patient should be given "as-needed" doses for the 
first 24 to 48 hours when a new drug is started to define the best daily 
dosing requirements for that individual patient. 

In addition to the titration of individual drugs, the modalities for 
pain management are titrated when the pain is persistent and is 
moderate to severe in intensity (see Figure 3). 

Pain management for moderate to severe pain should begin with 
oral opioids in combination with an NSAID or acetaminophen. The 
optimal dose will control pain with the fewest side effects, such as 
sedation, mental clouding, nausea, or constipation. 

Adjuvant drugs (see below) may be used to counteract the 
predictable side effects of opioids. For example, hydroxyzine may be 
added to opioids and NSAIDs to manage anxiety and nausea, espe- 
cially when they occur simultaneously and are not intense. Dietary 
caffeine supplementation may provide additive analgesia and counter- 
act opioid induced sedation. Antiemetic drugs such as phenothiazines 
and metoclopramide may be added to manage opioid-induced nausea. 

It is usually advisable to observe the patient's response to several 
different opioids, sequentially, before switching routes of administration 
or trying an anesthetic, neurosurgical, or other invasive approach to 
relieve persistent pain (Galer, Coyle, Pasternak, et al., 1992). For exam- 
ple, patients who experience dose-limiting sedation, nausea, or mental 
clouding on oral morphine should be switched to an equianalgesic dose 
of hydromorphone or fentanyl. The dose of the second opioid should 
then be adjusted. Sequential analgesic trials should be based on regular 



oral and parenteral doses because of pharmacokinetic differences. 

transdermal fentanyl (Duragesic) is an alternative option. Transdermal fentanyl dosage is not 
calculated as equianalgesic to a single morphine dose. See the package insert for dosing 
calculations. Doses above 25 ^g/h should not be used in opiod-naive patients. 
5 Caution: Doses of aspirin and acetaminophen in combination opioid/NSAID preparations 
must also be adjusted to the patient's body weight. Aspirin is contraindicated in children in 
the presence of fever or other viral disease because of its association with Reye's syndrome. 
6 Caution: Codeine doses above 65 mg often are not appropriate because of diminishing 
incremental analgesia with increasing doses but continually increasing nausea, constipation, 
and other side effects. 

Note: Published tables vary in the suggested doses that are equianalgesic to morphine. Clini- 
cal response is the criterion that must be applied for each patient; titration to clinical 
responses is necessary. Because there is not complete cross-tolerance among these drugs, 
it is usually necessary to use a lower than equianalgesic dose when changing drugs and to 
retitrate to response. 

Codes: q=every. N/A=not available. N/R=not recommended. IM=intramuscular. 
SC=subcutaneous. 



53 



Table 1 1 . Dose equivalent for opioid analgesics in 
opioid-naive children and adults <50 kg body weight 1 



Drug 


Approximate 
equianalgesic dose 


Usual starting dose 

for moderate to 

severe pain 




Oral 


Parenteral 


Oral 


Parenteral 


Opioid agonist 2 


Morphine 3 


30 mg q 3-4 h 
(repeat around- 
the-clock 
dosing) 

60 mg q 3-4 h 
(single dose or 
intermittent 
dosing) 


10 mg 
q3-4h 


0.3 mg/kg 
q3-4h 


0.1 mg/kg 
q3-4h 


Morphine 
controlled-release 34 
(MS Contin, 
Oramorph) 


90-120 mg 
q12h 


N/A 


N/A 


N/A 


Hydromorphone 3 
(Dilaudid) 


7.5 mg 
q3-4h 


1.5 mg 
q3-4h 


0.06 mg/kg 
q3-4h 


0.015 mg/kg 
q3-4h 


Levorphanol 
(Levo-Dromoran) 


4mg 
q6-8h 


2mg 
q6-8h 


0.04 mg/kg 
q6-8h 


0.02 mg/kg 
q6-8h 


Meperidine 
(Demerol) 


300 mg 
q2-3h 


100 mg 
q3h 


N/R 


0.75 mg/kg 
q2-3h 


Methadone 

(Dolophine, others) 


20 mg 
q6-8h 


10mg 
q6-8h 


0.2 mg/kg 
q6-8h 


0.1 mg/kg 
q6-8h 


Combination opioid) 


r NSAID preparations 5 






Codeine 6 (with aspirin 
or acetaminophen) 


180-200 mg 
q3-4h 


130 mg 
q3-4h 


0.5-1 mg/kg 
q3-4h 


N/R 


Hydrocodone (in 
Lorcet, Lortab, 
Vicodin, others) 


30 mg 
q3-4h 


N/A 


0.2 mg/kg 
q3-4h 


N/A 


Oxycodone 

(Roxicodone, also in 
Percocet, Percodan, 
Tylox, others) 


30 mg 
q3-4h 


N/A 


0.2 mg/kg 
q3-4h 


N/A 



1 Caution: Doses listed for patients with body weight less than 50 kg cannot be used as initial 
starting doses in babies less than 6 months of age. 

2 Caution: Recommended doses do not apply to patients with renal or hepatic insufficiency or 
other conditions affecting drug metabolism and kinetics. 

3 Caution: For morphine, hydromorphone, and oxymorphone, rectal administration is an alter- 
nate route for patients unable to take oral medications. Equianalgesic doses may differ from 
oral and parenteral doses because of pharmacokinetic differences. 

4 Transdermal fentanyl (Duragesic) is an alternative option. Transdermal fentanyl dosage is not 
calculated as equianalgesic to a single morphine dosage. See the package insert for dosing 



54 



Pharmacologic Management 

assessments of pain, with continuous attention to antineoplastic and 
noninvasive nonpharmacologic therapies (see Figure 1). 

Administration Methods 



The speed of onset and duration of action for any opioid depend on 
the specific drug chosen and its formulation (tablet, elixir, etc.). Most 
are well absorbed after oral or rectal administration, yet absorption 
may not be complete. Further, drugs absorbed from the gut are subject 
to first-pass metabolism in the liver and, hence, should be given at 
higher doses than when given parenterally. Although dosage require- 
ments for different parenteral routes (intravenous, subcutaneous, and 
intramuscular) are comparable or equivalent, the onset of drug action 
is typically most rapid after intravenous dosing because there is no 
delay in absorption. Therefore, drug dose and frequency should be 
titrated to the individual patient's response and analgesic needs when 
changing the route of administration or the type of formulation. 

Oral. The oral route is the preferred route of analgesic adminis- 
tration because it is the most convenient and cost-effective. Oral 
opioids are available in tablet, capsule, and liquid forms and in imme- 
diate and controlled-release formulations; morphine is available in 
immediate and controlled-release forms. Controlled-release tablets 
become immediately released when crushed and are therefore not 
appropriate for patients who are unable to swallow whole tablets. A 
small percentage may require alternate routes during their illness and 
when they are unable to swallow, such as during mucositis or in the 
terminal phase. Coyle, Adelhardt, Foley, et al. (1990) found that many 
patients required more than one route of administration to maintain 
pain control in the last 4 weeks of life. When patients cannot take 
medications orally, other less invasive routes such as rectal or transder- 
mal routes should be tried. During intravenous and subcutaneous 
administration, local irritation of the skin or vein may occur. Therefore, 



calculations. Doses above 25 |xg/h should not be used in opioid-naive patients. 
5 Caution: Doses of aspirin and acetaminophen in combination opioid/NSAID preparations 
must also be adjusted to the patient's body weight. Aspirin is contraindicated in children in 
the presence of fever or other viral disease because of its association with Reye's syndrome. 
6 Caution: Some clinicians recommend not exceeding 1 .5 mg/kg of codeine because of an 
increased incidence of side effects with higher doses. 

Note: Published tables vary in the suggested doses that are equianalgesic to morphine. Clini- 
cal response is the criterion that must be applied for each patient; titration to clinical 
responses is necessary. Because there is not complete cross-tolerance among these drugs, it 
is usually necessary to use a lower than equianalgesic dose when changing drugs and to reti- 
trate to response. 

Codes: q=every. N/A=not available. N/R=not recommended. 

55 



Management of Cancer Pain 

parenteral routes should be used only when simpler, less demanding, 
and less costly methods are inappropriate or ineffective. 

Rectal. The rectal route may be used when patients have nausea 
or vomiting or are fasting either preoperatively or postoperatively. 
The rectal route is contraindicated if there are lesions of the anus or 
rectum because placement of the suppository will cause pain. This 
route is also not useful if there is diarrhea or in elderly or infirm 
patients who are physically unable to place the suppository. 

There are commercially available suppositories of morphine, hydro- 
morphone, and oxymorphone. Medications can also be placed in a 
colostomy or similar stoma, provided that the flow of effluent is slow 
enough to allow the drug to be absorbed via the mucosa (McCaffery, 
Martin, and Ferrell, 1992). When converting from the oral to the rectal 
route, start with the same amount as the oral dose and titrate as needed. 

Transdermal. Transdermal administration bypasses GI absorption. 
Fentanyl is currently the only opioid commercially available in a trans- 
dermal form (TDS-Fentanyl). Four patch sizes are available and pro- 
vide delivery of fentanyl at 25, 50, 75, or 100 jxg/hour; therefore, there is 
flexibility in drug dosing. The maximal recommended daily dose is 300 
|jLg/hour. Patients requiring larger doses should be switched to an 
equianalgesic dose of an oral or subcutaneously administered opioid. 

Each patch contains a 72-hour supply of fentanyl, which is passively 
absorbed through the skin over this period. Levels in plasma rise slowly 
over 12 to 18 hours after patch placement, and the dosage form has an 
elimination half-life of 21 hours. Therefore, unlike intravenous fentanyl, 
the transdermal administration of fentanyl is not suitable for rapid dose 
titration (Payne, 1992; Portenoy, Southam, Gupta, et al., 1993). Trans- 
dermal fentanyl should be considered when patients already on opioid 
therapy have relatively constant pain and infrequent episodes of break- 
through pain such that rapid increases or decreases in pain intensity are 
not anticipated. As with other long acting analgesics, all patients should 
be provided with oral or parenteral rapidly acting short duration 
opioids to manage breakthrough pain (Portenoy and Hagen, 1990). The 
most commonly reported side effects of transdermal fentanyl adminis- 
tration are nausea, mental clouding, and skin irritation. 

Nasal. The transnasal route is an alternative delivery method that 
may be useful when patients are no longer able to tolerate the oral 
route. Although several agents are currently being studied, the only 
commercially available formulation is the mixed agonist-antagonist 
drug butorphanol, which is rapidly taken up by the vascular nasal 
mucosa. The major indication for its use is acute headache. Although 
this formulation has general appeal by virtue of its potential for rapid 
action because it is a mixed agonist-antagonist, this drug is not recom- 
mended for routine use in cancer pain treatment. 

56 



Pharmacologic Management 

Intravenous or Subcutaneous. Intramuscular administration of 
drugs should be avoided because this route can be painful and incon- 
venient, and absorption is not reliable. Intravenous or subcutaneous 
administration are effective alternatives. Patients who may benefit 
from continuous infusions of opioids include: 

■ Those with persistent nausea and vomiting. 

■ Those with severe dysphagia or swallowing disorders. 

■ Those with delirium, confusion, stupor, or other mental status 
changes that make oral administration contraindicated because of 
concerns about pulmonary aspiration in an unprotected airway. 

■ Those on high doses of oral medications necessitating numerous 
tablets. 

■ Those who experience undesirable side effects in relation to each 
dose of an "as-needed" medication. 

■ Those who require rapid incremental doses of analgesia. 

The benefits of opioid infusions, compared with those of intermit- 
tent "as-needed" doses by intramuscular or subcutaneous injection, 
include less pain on injection, fewer delays awaiting preparation and 
administration of medication, and improved effectiveness (Bruera, 
Brenneis, and MacDonald, 1987; Portenoy, 1986, 1987). The intra- 
venous route provides the most rapid onset of analgesia, but the dura- 
tion of analgesia after a bolus dose is shorter than with other routes. 

A continuous intravenous infusion provides the most consistent 
level of analgesia and is easily accomplished for patients who have 
permanent intravenous access for other purposes such as hydration, 
alimentation, chemotherapy, or antibiotic administration. If intra- 
venous access is not available or desirable, continuous subcutaneous 
opioid infusion offers a practical alternative in the hospital and home. 
The subcutaneous administration of opioids provides levels in blood 
comparable to those with intravenous doses; therefore, the intra- 
venous dose recommendations can be used (Tables 10 and 11) 
(Moulin, Kreeft, Murray-Parsons, et al., 1991). 

Intraspinal. Analgesics may be administered intraspinally when 
pain cannot be controlled by oral, transdermal, subcutaneous, or intra- 
venous routes because side effects such as confusion and nausea limit 
further dose escalation. Documentation of the failure of maximal doses 
of opioids and coanalgesics administered through other routes should 
precede consideration of intraspinal analgesia. Furthermore, this route 
requires experience, meticulous technique, significant family and 
professional support systems, and sophisticated followup, which are 
not available in all settings. Before implantation of a permanent 

57 



Management of Cancer Pain 

device, screening should be conducted to ensure adequate response to 
spinal therapy. A trial of graded opioid doses administered percuta- 
neously through an epidural catheter generally will indicate whether 
intraspinal therapy is warranted. 

As with systemic opioid administration, the dose range for 
intraspinal opioid therapy varies widely, depending on the level of 
pain and tolerance (Du Pen and Williams, 1992). Any agent delivered 
into the epidural or intrathecal space should be free of preservatives 
because some preservatives and antioxidants can produce neurotoxic- 
ity when used intraspinally (Du Pen, Ramsey, and Chin, 1987; Wang, 
Hillman, Spielholz, et al., 1984). All patients treated with intraspinal 
drugs should have access to rescue medications (oral or parenteral) 
for periods of breakthrough pain or in the case of catheter or drug 
delivery system malfunction. The coadministration of systemic opioids 
(which generally is not recommended for postoperative pain manage- 
ment) is safe in most cancer patients because they are tolerant to the 
respiratory-depressant effects of the drugs. 

Morphine is the most commonly used intraspinal drug. Alterna- 
tive opioids such as hydromorphone, fentanyl, or sufentanil have been 
used intraspinally to manage cancer pain and may be useful substi- 
tutes when the patient experiences side effects from morphine. 
Intraspinal morphine may produce the same side effects of nausea, 
mental clouding, and sedation as in oral, rectal, or parenteral dosing, 
because epidural or subarachnoid morphine is absorbed into the circu- 
lation by way of the rich epidural vascular plexus and is also carried in 
the normal flow of cerebrospinal fluid (CSF) from spinal levels to the 
brain (Bromage, Camporesi, Durant, et al., 1982; Chauvin, Samii, 
Schermann, et al., 1982; Cousins, 1988; Max, Inturrisi, Kaiko, et al., 
1985). Single-dose epidural administration of 10 mg of morphine 
produces levels in blood comparable to an intramuscular injection of 
the same dose (Max, Inturrisi, Kaiko, et al., 1985). Very lipophilic 
opioids such as fentanyl and sufentanil have a more limited CSF distri- 
bution, but these drugs also gain access to the blood and are delivered 
to the brain via the systemic circulation. 

In some patients, it is possible to give relatively small doses of 
opioid spinally and produce pain relief while avoiding the side effects 
that can limit prior oral or parenteral dosing. However, patients with a 
high degree of tolerance to systemic opioids may require large doses 
of spinal opioids (Cousins and Bridenbaugh, 1987), which may negate 
the advantages of this targeted approach because side effects may still 
be prominent at high dosage levels. 

The main indication for the long-term administration of 
intraspinal opioids is intractable pain in the lower part of the body, 
particularly when pain is bilateral or midline (Du Pen and Williams, 
1992). With proper selection and screening, good to excellent pain 

58 



Pharmacologic Management 

relief can be expected in up to 90 percent of patients (Krames, 
Gershow, Glassberg, et al., 1985; Onofrio and Yaksh, 1990). Opioids 
(sometimes coadministered with other agents such as dilute local 
anesthetic) (Akerman, Arwestrom, and Post, 1988; Fraser, Chapman, 
and Dickenson, 1992; Maves and Gebhart, 1992; Tejwani, Rattan, and 
McDonald, 1992) are delivered to the epidural or subarachnoid space 
via percutaneously placed catheters connected to ports, reservoirs, or 
infusion pumps (Table 12). For short-term treatment of weeks to a few 
months, externalized catheters (tunneled or untunneled) can be used. 
For more prolonged treatment, the delivery system (catheter plus port 
or pump) can be internalized. Adverse sequelae include the develop- 
ment of tolerance, urinary retention, constipation, pruritus, device 
failure, and infection (Du Pen, Peterson, Williams, et al., 1990; Hogan, 
Haddox, Abram, et al., 1991). 

Intraventricular. Experience with intraventricular morphine 
administration is steadily increasing, and results with this route 
compare favorably with those with intraspinal administration, with 
over 90 percent of patients in published series benefitting significantly 
(Choi, Ha, Ahn, et al., 1989). Most important, intraventricular 
morphine is beneficial for recalcitrant pain due to head and neck 
malignancies and tumors (e.g., superior sulcus tumors, breast carci- 
noma) that affect the brachial plexus. Small maintenance doses of 
morphine (less than 5 mg daily) are needed to achieve maximal 
comfort. Complications are rare, the most important being infection; 
as with intraspinal drug delivery, tolerance and respiratory depression 
do not appear to be major issues (Acute Pain Management Guideline 
Panel, 1992). Intraventricular morphine requires the placement of a 
ventricular catheter connected to a subcutaneous (e.g., Ommaya) 
reservoir for intermittent administration or an infusion pump for 
continuous infusion (Lazorthes, Verdie, Bastide, et al., 1985; Obbens, 
Hill, Leavens, et al., 1987). 

Patient-Controlled Analgesia (PCA). PCA allows patients to 
control the amount of analgesia they receive (Ferrante, Ostheimer, 
and Covino, 1990). PCA can be accomplished by mouth or by the use 
of a special pump set to prescribed parameters to administer the drug 
intravenously, subcutaneously, or epidurally. In contrast to the use of 
PCA in postoperative pain management, the majority of the opioid 
dose is usually delivered via continuous systemic infusion. Patient- 
administered boluses are required to treat breakthrough pain and to 
provide a basis for more accurate and rapid upward titration of the 
continuous infusion rate. 

Intravenous or subcutaneous PCA allows patients to accommo- 
date transient changes in analgesic requirements (such as during 
dressing changes or positioning) and to tailor analgesic doses accord- 
ing to their own requirements. PCA is also useful in controlling pain 

59 



Management of Cancer Pain 

Table 12. Intraspinal drug delivery systems 



System 


Advantages 


Disadvantages 


Percutaneous 
temporary catheter 


Used extensively 
both intraoperatively 
and postoperatively. 
Useful when prognosis is 
limited (< 1 month). 


Mechanical problems 
include catheter 
dislodgment, kinking, 
or migration. 


Permanent 

silicone-rubber 

epidural 


Catheter implantation is 
a minor procedure. 
Dislodgment and infection 
less common than with 
temporary catheters. 
Can deliver bolus injections, 
continuous infusions, or 
PCA (with or without 
continuous delivery). 




Subcutaneous 
implanted 
injection port 


Increased stability, less risk 
of dislodgment. 
Can deliver bolus injections 
or continuous infusions 
(with or without PCA). 


Implantation more invasive 
than external catheters. 
Approved only for epidural 
catheter in U.S. 
Potential for infection 
increases with frequent 
injections. 


Subcutaneous reservoir 


Potentially, reduced infection 
in comparison to external 
system. 


Difficult to access, and 
fibrosis may occur after 
repeated injection. 


Implanted pumps 
(continuous and 
programmable) 


Potentially, decreased 
risk of infection. 


Need for more extensive 
operative procedure. 
Need for specialized, 
costly equipment with 
programmable systems. 



quickly in the patient admitted to the hospital specifically for analge- 
sia, and in determining the opioid dosage requirements for conversion 
to an oral regimen once a steady level of satisfactory analgesia is 
attained (Baumann, Batenhorst, Graves, et al., 1986). Intravenous and 
subcutaneous PCA is safe for both home and hospitalized patients 
(Baumann, Batenhorst, Graves, et al., 1986; Citron, Johnston-Early, 
Boyer, et al., 1986; Kerr, Sone, Deangelis, et al., 1988; Swanson, Smith, 
Bulich, et al., 1989) but is contraindicated for sedated and confused 
patients (Ferrell, Cronin Nash, and Warfield, 1992). 



60 



Pharmacologic Management 

Management of Side Effects 

Constipation and sedation are the most common side effects asso- 
ciated with opioids; others include confusion, nausea and vomiting, 
respiratory depression, dry mouth, urinary retention, pruritus, 
myoclonus, altered cognitive function, dysphoria, euphoria, sleep 
disturbances, sexual dysfunction, physiologic dependence, tolerance, 
and inappropriate secretion of antidiuretic hormone (Table 13). 
Because there is great individual variation in the development of 
opioid-induced side effects, clinicians should monitor for them and 
prophylactically treat some inevitable ones. 

Constipation. Constipation is a common problem associated with 
opioid administration. Tolerance to the constipating effects of opioids 
either does not occur or occurs very slowly during chronic therapy. 
Constipation may worsen with time because of the disease process 
(e.g., intestinal obstruction, paralytic ileus due to spinal cord compres- 
sion, decreased food and fluid intake due to anorexia); therefore a 
careful search for other causes should be performed (Glare and 
Lickiss, 1992). Mild constipation can usually be managed by an 
increase in fiber consumption and the use of a mild laxative such as 
milk of magnesia. These cathartic agents should be administered on a 
regular schedule, barring contraindications. Severe constipation 
occurs as a result of the inhibition of peristalsis by opioids and can be 
treated with a stimulating cathartic drug, e.g., bisacodyl, standardized 
senna concentrate, or hyperosmotic agents (e.g., lactulose or sorbitol). 
Oral laxatives can be taken at bedtime, and rectal suppositories can be 
used in the morning if needed. 

Stool softeners or emollient laxatives, e.g., docusate, are of limited 
usefulness because of colonic resorption of water from the forming 
stool. They should not be used as the sole regimen but may be useful 
when given in combination with stimulant laxatives to ease defecation, 
especially in bedridden patients (Levy, 1991). 

Sedation. Transitory sedation is common when opioid doses are 
increased substantially, but tolerance usually develops rapidly. Persis- 
tent drug-induced sedation is usually best treated by reducing the 
opioid in each dose and increasing the dosage frequency. This strategy 
will decrease the peak concentrations in blood (and brain) while 
maintaining the same total dose. In some patients, switching to 
another opioid may reduce the sedative effects. CNS stimulants such 
as caffeine, dextroamphetamine (2.5 to 7.5 mg twice daily, orally), 
pemoline (18.5 to 37 mg, orally), or methylphenidate (5 to 10 mg, 
orally) (Bruera, Brenneis, and Paterson, 1989) may be added to 
increase alertness if the above approach is ineffective in reducing 
sedation (Forrest, Brown, Brown, et al., 1977). 

61 



Table 13. General comments and cautions regarding 
the use of opioid analgesics 

■ Drugs of choice for severe cancer-related pain. Opioids do not have an anal- 
gesic ceiling effect, and therefore, dose can be titrated to achieve maximum 
pain relief. 

■ Constipation is an almost universal complication of opioid use, so ali patients 
should receive prophylactic stimulant laxative therapy unless otherwise 
contraindicated (e.g., chronic diarrhea). 

■ Sedation is a frequent side effect of initial opioid use; however, tolerance 
develops soon in most patients. 

■ Respiratory depression rarely occurs except in opioid-naive patients and those 
with significant pulmonary disease. 

■ True hypersensitivity reactions to opioids are rare. If patients experience such 
reactions, it is often possible to administer an opioid from another subclass 
safely. 

The subclasses are: Phenanthrene derivatives: morphine, codeine, 
hydromorphone, oxycodone. Phenylpiperidine derivatives: meperidine, 
fentanyl. Diphenylheptane derivatives: methadone. 

■ The use of opioid antagonists such as naloxone can immediately reverse all 
opioid effects including analgesia. Such reversal results in acute withdrawal, 
which may be complicated by excruciating pain and seizure. Therefore, opioid 
antagonists are never recommended to reverse non-life-threatening effects 
such as confusion or sedation. If used to reverse life-threatening respiratory 
depression or hypotension, they should be titrated cautiously. 

■ Oral is the preferred route of administration, except for patients who cannot 
take or tolerate oral medications. When given in appropriate doses, oral 
opioids are as efficacious as parenteral opioids. 

■ Rectal and transdermal dosage forms are available and effective noninvasive 
alternatives when oral medication is not possible. 

Rectal suppositories are contraindicated if lesions of the rectum or anus 
are present. 

■ Repetitive intramuscular and subcutaneous (SC) injections should be avoided 
because they are painful and absorption is inconsistent. 

■ Intravenous (IV) administration may be used when less invasive routes are inef- 
fective or unavailable. IV opioids may be given by bolus or continuous adminis- 
tration (including PCA); however, they require careful monitoring during titra- 
tion. Inappropriately excessive dosing may carry significant risk of respiratory 
depression, especially in opioid-naive patients or those with underlying 
pulmonary pathology. 

Low-volume continuous SC infusion may also be used if venous access is 
not established. 

■ IV or SC PCA provides a good steady level of analgesia. It is widely accepted 
by patients but requires special infusion pumps and staff education. May not 
be appropriate for patients with altered mental status or agitation. 

■ Epidural and intrathecal opioids provide good analgesia, when suitable. These 
routes have significant risk of respiratory depression, which may be delayed, 
necessitating careful monitoring. Special preservative-free drug formulations 
are necessary for these routes of administration. 



62 



Pharmacologic Management 

These agents also improve the cognitive function of patients 
receiving opioids, most likely by counteracting the sedation. In these 
patients, methylphenidate has been demonstrated to improve func- 
tioning on a number of neuropsychological tests, including tests of 
memory, mental speed, and concentration (Bruera, Miller, Macmillan, 
et al., 1992). 

Nausea and Vomiting. There are no controlled studies that estab- 
lish the indications, efficacy, and dosing requirements for treatment of 
opioid-induced nausea and vomiting. As with other side effects, it is 
important to determine the cause. Clinical experience suggests that 
opioid-induced nausea and vomiting can be managed with antiemetics 
chosen according to their modes of action. Metoclopramide is helpful 
when neuroleptics such as prochlorperazine, chlorpromazine, or 
haloperidol fail to control nausea and vomiting. Scopolamine or 
hydroxyzine may ameliorate symptoms as a result of their effects on 
the vestibular system. Scopolamine, which is an acetylcholine receptor 
antagonist, can be given transdermally to reduce nausea due to 
motion sickness (Ferris, Kerr, Sone, et al., 1991) or related to cancer. 
When patients complain of nausea after opioid administration has 
begun, it is often helpful to administer an antiemetic on a fixed sched- 
ule for several days, after which as-needed dosing is usually adequate 
(Portenoy, 1988). Depending on the antiemetic chosen, patients 
should be monitored for the possibility of increased sedation. 

Respiratory Depression. Patients receiving long-term opioid 
therapy usually develop tolerance to the respiratory-depressant effects 
of these agents. Occasionally, respiratory depression occurs when pain 
is abruptly relieved and the sedative effects of opioids are no longer 
opposed by the stimulating effects of pain (Hanks, Twycross, and 
Lloyd, 1981). In a symptomatic patient, physical stimulation may be 
enough to prevent significant hypoventilation. Opioid antagonists 
(e.g., naloxone) should be given cautiously to patients who are receiv- 
ing opioids on a long-term basis. Because patients who have become 
tolerant to opioids show great sensitivity to the effects of antagonist 
drugs, symptomatic respiratory depression should be treated carefully 
using a dilute solution of naloxone (0.4 mg in 10 mL of saline), admin- 
istered as 0.5 mL (0.02 mg) boluses every minute. The dose of nalox- 
one should be titrated to the patient's respiratory rate. A return to full 
alertness is often accompanied by a severe withdrawal syndrome and 
a return of pain. Naloxone titration, when indicated for the reversal of 
opioid-induced respiratory depression, should be given incrementally 
in doses that improve respiratory function but do not reverse analge- 
sia. Repeated doses may be required (American Pain Society, 1992; 
Portenoy, 1988), or alternatively, an infusion of two ampules (total, 
0.8 mg) in 250 mL of 5 percent dextrose in water may be continuously 
titrated toward this goal. 

63 



Management of Cancer Pain 

Far more common than acute respiratory depression is subacute 
overdose, in which sedation gradually builds and is followed by a 
slowing of respiratory rate and then by ventilatory failure. The degree 
of sedation rather than the respiratory rate is a better indicator of 
impending respiratory depression (Kaiko, Kanner, Foley, et al., 1987). 
The risk of this complication is highest during titration of opioids with 
long plasma half-lives, such as methadone and levorphanol, and is best 
managed by withholding one or two doses and then reducing the 
standing dose by 25 percent of its current level until symptoms have 
resolved. At that time, a cautious titration can be resumed. The main- 
tenance of 25 percent of the dose has been found to be adequate to 
prevent acute opioid withdrawal (American Pain Society, 1992). 

Clinicians are often concerned that high doses of opioids used for 
palliation may harm or kill a patient, particularly when doses are 
further increased to alleviate pain (Cain and Hammes, in press). This 
double effect of intended benefit and potential harm (Reich, 1992) is 
seen in the clinical situation when the intended treatment may have 
inextricably linked deleterious side effects. The administration of 
medication is always a risk-versus-benefit calculation. When the 
patient's death is imminent because of the progression of primary 
disease, an increased risk of earlier death counts little against the 
benefit of pain relief and painless death. The ethical duty to benefit 
the patient through relieving pain is by itself adequate to support 
increasing doses to alleviate pain, even if there might be life-shorten- 
ing and expected side effects. Because many patients in the terminal 
phase have been receiving opioid pain medications for a significant 
period of time, the fear of shortening life by medication is usually 
unfounded. Respiratory depression is not often a significant limiting 
factor in pain management because, with repeated doses, tolerance 
develops to this effect, allowing for adequate pain treatment with 
escalating doses without respiratory compromise (Foley, 1991). The 
person dying from cancer should not be allowed to live out life with 
unrelieved pain because of fear of side effects; rather, appropriate, 
aggressive palliative support should be given (see Shapiro, in press, b; 
Cain and Hammes, in press). 

Other Side Effects. Opioids occasionally cause myoclonus, 
seizures, hallucinations (Bruera, Schoeller, and Montejo, 1992), confu- 
sion, sexual dysfunction, sleep disturbances, and pruritus (Thangathu- 
rai, Bowles, Allen, et al., 1988). Prolonged use is known to affect 
sexual function and libido in both men and women. Women experi- 
ence amenorrhea and infertility, whereas men report an inability to 
attain or maintain an erection. Changes in serum testosterone and 
other sex hormones have been described and may be responsible for 
some of these effects (Abel, 1984). 

64 



Pharmacologic Management 

Urinary retention may also occur, especially with spinal opioids 
(Cousins and Mather, 1984; Dray, 1988; Moulin, Kreeft, Murray- 
Parsons, et al., 1991; Rawal, Mollefors, Axelsson, et al., 1983), in men 
with prostatism, or in patients with pelvic tumors and bladder outlet 
obstruction. The management of urinary retention may include 
discontinuing adjuvant drugs with potentiating effects (e.g., tricyclic 
antidepressants) or changing to another opioid analgesic or route of 
administration. Diphenhydramine, an antihistamine, may reduce 
pruritus in some patients. The syndrome of the inappropriate secre- 
tion of antidiuretic hormone is a rare, often transitory, adverse effect 
of opioid drugs, most commonly reported with morphine and 
methadone; more often, it is a paraneoplastic complication. 

Adjuvant Drugs 

Adjuvant drugs are used to enhance the analgesic efficacy of 
opioids, treat concurrent symptoms that exacerbate pain, and provide 
independent analgesia for specific types of pain. They may be used in 
all stages of the analgesic ladder. Commonly used agents are described 
below, with approximate daily dosage ranges listed in Table 14. 

Corticosteroids 

Corticosteroids provide a range of effects including mood eleva- 
tion, anti-inflammatory activity, antiemetic activity, and appetite stim- 
ulation. These effects may be beneficial in the management of 
cachexia and anorexia in terminal illness (Bruera, Roca, Cedaro, et 
al., 1985). They also reduce cerebral and spinal cord edema and are 
essential in the emergency management of elevated intracranial pres- 
sure and epidural spinal cord compression. Steroids are part of the 
standard therapy for tumor-induced spinal cord compression (Byrne, 
1992), and they are effective in reducing pain due to perineural edema 
and pressure on nerves. Dexamethasone (16 to 24 mg/day) or pred- 
nisone (40 to 100 mg/day) may be added to opioids for the manage- 
ment of pain in brachial or lumbosacral plexopathy. Undesirable 
effects such as myopathy, hyperglycemia, weight gain, and dysphoria 
may occur during prolonged steroid therapy. 

Anticonvulsants 

Anticonvulsants are used to manage neuropathic pain, especially 
when the pain is lancinating or burning. Phenytoin, carbamazepine, 
valproate, and clonazepam suppress spontaneous neuronal firing and 
are used to control lancinating pain complicating nerve injury (Swerd- 
low, 1984). Dose-related transient bone marrow suppression, which is 
associated with carbamazepine therapy (Horowitz, Patwardhan, and 

65 



Management of Cancer Pain 

Table 14. Adjuvant analgesic drugs for cancer pain 



Drug 


Approximate 
adult daily 
dose range 


Route of 
administration 1 


Type of pain 


Corticosteroids 


Dexamethasone 2 


16-96mg 


PO, IV 


Pain associated with brain 
metastases and epidural 
spinal cord compression 


Prednisone 


40-100 mg 


PO 


Anticonvulsants 


Carbamazepine 3 


200-1 ,600 mg 


PO 


Neuropathic pain 


Phenytoin 4 


300-500 mg 


PO 


Antidepressants 


Amitriptyline 5 


25-15 mg 


PO 


Neuropathic pain 


Doxepin 6 


25-150 mg 


PO 


Imipramine 7 


20-100 mg 


PO 


Trazodone 8 


75-225 mg 


PO 


Neuroleptics 


Methotrimeprazine 9 


40-80 mg 


IM 


Analgesia; sedation; 
antiemetic 


Antihistamines 


Hydroxyzine 10 


300-450 mg 


IM 


Adjuvant to opioids in 
post-operative and other 
types of pain; relief of 
complicating symptoms 
including anxiety, 
insomnia, nausea 


Local anesthestics/antiarrythmics 


Lidocaine 11 


5 mg/kg 


IV/SC 


Neuropathic pain 


Mexiletine 12 


450-600 mg 


PO 


Tocainide 13 


20 mg/kg 


PO 


Psychostimulants 


Dextroamphetamine 14 


5-10 mg 


PO 


Improve opioid analgesia, 
decrease sedation 


Methylphenidate 15 


10-15 mg 


PO 



1 PO=orally. IV=intravenously. IM=intramuscularly. SC=subcutaneously. 

2 French and Galicich, 1964; Greenberg, Kim, and Posner, 1980; Weissman, 1988. 

3 Lindstrom and Lindblom, 1987. 

4 Yajnik, Singh, Singh, et al., 1992. 

5 Max, Culnane, Schafer, et al., 1987; Max, Schafer, Culnane, et al., 1988; Onghena and 

66 



Pharmacologic Management 

Marcus, 1988; Pellock, 1987), requires that it be used with caution in 
cancer patients undergoing other marrow-suppressant therapies, such 
as chemotherapy and radiation therapy. Toxicity often correlates with 
high concentrations in serum, and levels in serum of phenytoin, 
valproate, and carbamazepine should be monitored routinely (for 
example, monthly in the stable patient). Systemically administered 
local anesthetic (intravenous lidocaine, oral mexilitine, and tocainide) 
and antiarrhythmic agents have been used clinically to treat neuro- 
pathic pain (Brose and Cousins, 1991; Dejgard, Petersen, and Kastrup, 
1988), although this is not currently an FDA-approved indication 
for these drugs. 

Antidepressants 

Tricyclic antidepressants are useful as adjuvant analgesics in the 
pharmacologic management of cancer pain, especially neuropathic 
pain. These drugs potentiate the analgesic effects of opioids in animal 
models of pain (Botney and Fields, 1983; Spiegel, Kalb, and Paster- 
nak, 1983) and have innate analgesic properties (Kishore-Kumar, 
Max, Schafer, et al., 1990; Max, Culnane, Schafer, et al., 1987). They 
are effective through mechanisms that include: (1) mood elevation 
(France, 1987), (2) potentiation or enhancement of opioid analgesia 
(Ventafridda, Bianchi, Ripamonti, et al., 1990), and (3) direct anal- 
gesic effects (Max, Schafer, Culnane, et al., 1988). 

The most widely reported experience has been with amitriptyline; 
therefore, it should be viewed as the tricyclic agent of choice, even 
though it produces anticholinergic side effects such as dry mouth, 
constipation, and urinary retention in many patients. Analgesic treat- 
ment failure may be due to low levels in serum (Max, Culnane, 
Schafer, et al., 1987; Max, Schafer, Culnane, et al., 1988). Doses of 
amitriptyline of up to 150 mg daily or higher may be required to obtain 
therapeutic effects (Kvinesdsal, Molin, Froland, et al., 1984; Watson 



Van Houdenhove, 1992; Turkington, 1980; Ventafridda, Bonezzi, Caraceni, et al., 1987; 

Watson and Evans, 1985; Watson, Evans, Reed, et al., 1982; Young and Clarke, 1985. 

6 Cohn, Machado, Bier, et al., 1988. 

7 Kvinesdal, Molin, Froland, et al., 1984; Turkington, 1980; Young and Clarke, 1985. 

8 Khurana, 1983; Ventafridda, Bonezzi, Caraceni, et al., 1987. 

9 Beaver, Wallenstein, Houde, et al., 1966; Rogers, 1989. 

10 Beaver and Feise, 1976; Bellville, Dorey, Capparell, et al., 1979; Glazier, 1990. 

11 Bach, Jensen, Kastrup, et al., 1990; Cousins and Brose, 1991. 

12 Dejgard, Petersen, and Kastrup, 1989. 

13 Lindstrom and Lindblom, 1987. 

14 Joshi, deJongh, Schnapper, et al., 1982. 

15 Bruera, Chadwick, Brenneis, et al., 1987. 

67 



Management of Cancer Pain 

and Evans, 1985). In the treatment of diabetic neuropathy pain, the 
therapeutic analgesic effects of amitriptyline appear to be correlated 
with concentrations in serum above 100 ng/mL. However, a corre- 
sponding relationship between amitriptyline concentrations in serum 
and analgesia has not been reported in cancer pain. 

The onset of analgesic effects occurs within 1 to 2 weeks after the 
start of therapy and peaks at 4 to 6 weeks (Max, Culnane, Schafer, et 
al., 1987; Max, Schafer, Culnane, et al., 1988; Pilowsky, Hallett, 
Bassett, et al., 1982). Treatment should be initiated with a small dose 
of amitriptyline (10 to 25 mg at bedtime), especially in debilitated 
patients, and increased slowly by 10 to 25 mg every 2 to 4 days toward 
150 mg. This approach takes advantage of the sedative effects of the 
drug and minimizes the risk of falling (especially in elderly patients) 
because of orthostatic hypotension. Amitriptyline is also useful when 
sleep disturbance complicates the presence of pain and depression, 
because its initial use is commonly associated with sedation. 

Neuroleptic Agents 



Neuroleptics, which include the major tranquilizers generally used 
to treat psychoses and other psychiatric disorders, have also been used 
as adjunctive analgesics. Methotrimeprazine is a phenothiazine that 
has analgesic properties. Intramuscular doses of 15 mg methotri- 
meprazine and 10 mg of morphine are equianalgesic (Lasagna and De 
Kornfeld, 1961). This phenothiazine analgesic lacks opioid-inhibitory 
effects on gut motility and probably produces analgesia through a- 
adrenergic blockade (Beaver, Wallenstein, Houde, et al., 1966). In 
patients who are opioid tolerant or who are experiencing dose-limiting 
opioid side effects, especially intractable constipation, it is an alterna- 
tive analgesic approach. It also has antiemetic and anxiolytic effects. 

Methotrimeprazine can produce sedation and hypotension and 
should be given cautiously. Although it is approved only for intramus- 
cular administration, clinicians have experience with oral and slow 
intravenous infusion to manage delirium, restlessness, and agitation in 
patients near death. Other phenothiazines have not been demonstrated 
to have analgesic properties (Maltbie, Cavenar, Sullivan, et al., 1979). 

Hydroxyzine 

Hydroxyzine is a mild anxiolytic agent with sedating and analgesic 
properties that is used in treating the anxious patient with pain (Beaver 
and Feise, 1976). This antihistamine also has antiemetic activity. 

68 



Pharmacologic Management 

Bisphosphonates and Calcitonin 

Severe bone pain is a frequent complication of bone metastases. 
For example, Galasko (1972) reported that 65 percent of patients with 
bone metastases from breast cancer experience bone pain. Bone pain is 
probably caused by osteoclast-induced bone resorption by the tumor, 
which may also result in osteoporosis, hypercalcemia, microfractures, 
or pathologic fractures (Ascari, Attardo-Parrinello, and Merlini, 1989). 
Bisphosphonates (e.g., etidronate, pamidronate) are analogues of 
endogenous pyrophosphates, which inhibit bone resorption in vivo 
(Fleish, Russel, and Francis, 1969). Pamidronate and etidronate are 
currently available for the management of hypercalcemia associated 
with malignancy. Anecdotal reports and early clinical trials have 
reported relief of bone pain or decreased analgesic use after the initia- 
tion of a bisphosphonate (Delmas, Charhon, Chapuy, et al., 1982; 
Elomaa, Blomqvist, Grohn, et al., 1983). Other researchers have 
described similar findings with bisphosphonates that are not available 
in the United States (Attardo-Parrinello, Merlini, Pavesi, et al., 1987; 
van Holten-Verzantvoort, Zwinderman, Aaronson, et al., 1991). Smith 
(1989), however, reported no difference in symptomatic relief or anal- 
gesic requirements in 57 patients with advanced hormone-refractory 
prostate cancer treated with etidronate or placebo. 

Calcitonin is also a potent inhibitor of osteoclast-induced bone 
resorption and, like the bisphosphonates, is used in the management 
of hypercalcemia of malignancy. At least one double-blind, random- 
ized trial comparing salmon calcitonin to placebo demonstrated that 
100 IU/day subcutaneously resulted in reduced analgesic consump- 
tion, shorter duration of pain, and subjective improvement (Roth and 
Kolaric, 1986). 

Although these agents that inhibit bone resorption appear to be 
beneficial in some patients with painful bone metastases, other 
patients have failed to respond. Additional studies are warranted to 
define criteria that may predict a clinical response to these drugs and 
to define further their optimal use in this setting. 

Placebos 

A mention of the placebo response is important to highlight the 
potentially harmful misunderstanding surrounding this phenomenon. 
The placebo response is common, and placebo-derived analgesia may 
be mediated to a great extent through endogenous opioid pathways. 
The deceptive use of placebo response to distinguish psychogenic pain 
from "real" pain should be avoided. Placebos are effective in a 
portion of patients for a short period of time only and should not be 
used in the management of cancer pain (American Pain Society, 1992; 
Foley, 1985a; World Health Organization, 1990). 

69 



Management of Cancer Pain 

Antineoplastic Therapies 

Antineoplastic treatments for cancer include chemotherapy, 
hormonal and biologic therapies, and radiotherapy. Chemotherapy 
and hormonal therapies are generally used to treat all sites of cancer 
throughout the body and are not used specifically to treat pain. 
However, when the cause of cancer pain is direct tumor involvement, 
antineoplastic treatments may produce analgesia if they cause signifi- 
cant tumor shrinkage. 

The major goal of antineoplastic treatment is either to cure by 
complete elimination of the cancer or, in situations in which cure is 
not possible, to prolong life and to achieve palliation of the tumor 
symptoms. Most important, the patient and clinician should discuss 
openly and thoroughly the expected goals and potential side effects of 
these therapies. 

Influence of Concurrent Medical Conditions 
on Pharmacotherapy 

The presence of other medical conditions in cancer patients and 
the medications taken for them may influence the choice of analgesic 
regimen for pain management. Common medications or classes of 
medications that produce clinically significant drug interactions with 
opioid analgesics include alcohol (as in elixirs) and other CNS depres- 
sants such as phenytoin, as well as rifampin (Kreek, Garfield, Gutjahr, 
et al., 1976) and monoamine oxidase inhibitors such as phenylzine 
sulfate and isocarboxazid (Breitbart and Holland, 1988). 

Coexisting conditions also may influence the type and doses of 
opioid analgesics administered. For example, patients with newly 
recognized cancer pain who have been recently treated with opioids 
for another reason, such as surgery, may require higher than the 
recommended starting doses because they are opioid tolerant. Coagu- 
lopathy, neutropenia, and sepsis may contraindicate the use of 
epidural catheters or other regional anesthetic techniques because the 
risks of bleeding or "seeding" of infection are increased. 

Many patients with cancer undergo surgery as part of their treat- 
ment. GI procedures such as gastrectomy and colectomy may 
markedly affect drug absorption and increase GI intolerance to some 
oral drugs. Drug pharmacokinetics can change after surgery because 
of changes in drug absorption and distribution caused by alterations in 
body weight, cardiac output, venous capacitance, extravascular fluid 
shifts, and protein binding. Fever and sepsis in the postoperative 
period can affect drug disposition, as do shock or trauma. Patients 
with such conditions may require higher than expected doses of 

70 



Pharmacologic Management 

opioids because of severe acute pain. In addition, they may not 
achieve clinically effective concentrations of opioids in plasma after 
intramuscular and subcutaneous injections because of the pharmaco- 
kinetic alterations described above. 

Cancer often occurs in the elderly, who usually have decreased 
renal function as a normal result of aging. Mild age-related renal 
insufficiency (decline in glomerular filtration rate) can impede the 
excretion of the biologically active metabolites of many opioids, 
resulting in clinically significant sedation and respiratory depression 
(Sear, Hand, Moore, et al., 1989), as well as nausea (Hagen, Foley, 
Cerbone, et al., 1991). Meperidine, methadone, levorphano, penta- 
zocine, and propoxyphene have increased bioavailability, prolonged 
half-lives, and decreased systemic clearance and thus accumulate in 
patients with hepatic or renal dysfunction. Renal excretion is a major 
route of elimination not only for opioids but also for their pharmaco- 
logically active metabolites norpropoxyphene, normeperidine, 
morphine-6-glucuronide, and dihydrocodeine. Hence, in patients with 
renal dysfunction, doses of the parent compounds should be lowered 
or given less frequently. 

Pharmacologic Treatments Not Recommended 

A number of drugs and routes of administration are not recom- 
mended for the relief of cancer pain. These are summarized in Table 15. 

Discharge Planning Regarding Medications 

Patients and their families may have difficulty in understanding 
and remembering the details of the plan for managing pain. Therefore, 
patients should be given a written pain management plan (Figure 5, see 
page 74). Pertinent instructions related to the management of pain 
include the specific drugs to be taken; the type and purpose of pain 
medication (e.g., opioid, tricyclic antidepressant, anxiolytic); the 
frequency of drug administration, with an emphasis in most cases on 
taking the medication around the clock rather than as needed; poten- 
tial side effects of each pain medication (particularly constipation for 
opioids) and a plan for their prevention or treatment; potential drug 
interactions; specific precautions to follow when taking a pain medica- 
tion, such as physical activity limitations and dietary restrictions; and 
whom to notify about pain problems or concerns about the medication. 

The plan should be reviewed with the patient, and the patient 
and/or caregiver should be given an opportunity to discuss fears or 
concerns about the use of opioid analgesics; to clarify issues related to 
tolerance, dependence, and addiction; to voice concerns about side 

71 



Management of Cancer Pain 

Table 15. Drugs and routes of administration not recommended 
for treatment of cancer pain 



Class 


Drug 


Rationale for not recommending 


Opioids 


Meperidine 


Short (2-3 hour) duration. Repeated administration 
may lead to CNS toxicity (tremor, confusion, or 
seizures) (Cleeland, 1985; Kaiko, Foley, Grabinski, 
et al., 1983; Szeto, Inturrisi, Houde, et al., 1977). 
High oral doses required to relieve severe pain, 
and these increase the risk of CNS toxicity (Ameri- 
can Pain Society, 1992; Weissman, Burchman, 
Dinndorf, et al., 1992). 


Miscellaneous 


Cannabinoids 


Side effects of dysphoria, drowsiness, hypoten- 
sion, and bradycardia preclude its routine use as 
an analgesic (American Pain Society, 1 992). 


Cocaine 


Has demonstrated no efficacy as an analgesic or 
coanalgesic in combination with opioids (Ameri- 
can Pain Society, 1992). 


Opioid 
agonist- 
antagonists 


Pentazocine 
Butorphanol 
Nalbuphine 


Risk of precipitating withdrawal in opioid- 
dependent patients. Analgesic ceiling 
(Kallos and Caruso, 1979; Nagashima, 
Karamanian, Malovany, et al., 1976). Possible 
production of unpleasant psychomimetic effects 
(e.g., dysphoria, hallucinations) (American 
Pain Society, 1992; Martin, 1984; Weissman, 
Burchman, Dinndorf, et al., 1992). 


Partial agonist 


Buprenorphine 


Analgesic ceiling. Can precipitate withdrawal 
(American Pain Society, 1992; Weissman, Burch- 
man, Dinndorf, et al., 1992). 


Antagonist 


Naloxone 
Naltrexone 


May precipitate withdrawal. Limit use to treatment 
of life-threatening respiratory depression 
(Ellison,1993). 



effects; and to discuss when it is appropriate to communicate with a 
clinician regarding the need for a change in the plan. 

Discharge planners should advise patients and clinicians to 
communicate the plan to other clinicians when the patient is being 
transferred from one health care setting to another, such as being 
discharged from an acute care facility to a hospice, in order to main- 
tain continuity in pain management. Attachment B contains examples 
of forms that patients can use at home to document their pain. 



72 



Pharmacologic Management 



Class 


Drug 


Rationale for not recommending 


Combination 
preparations 


Brompton's 
cocktail 


No evidence of analgesic benefit to using 
Brompton's cocktail over single opioid 
analgesics (Twycross, 1977; Walsh, 1984; Weiss- 
man, Burchman, Dinndorf, et al., 1992; Wisconsin 
Cancer Pain Initiative, 1988). 


DPT (Meperidine, 
Promethazine, 
and 
Chlorpromazine) 


Efficacy is poor compared with that of other 
analgesics. High incidence of adverse effects 
(Nahata, Clotz, and Krogg, 1985). 


Anxiolytics alone 


Benzodiazepine 

(e.g., 

alprazolam) 


Analgesic properties not demonstrated 
except for some instances of neuropathic 
pain. Added sedation from anxiolytics may limit 
opioid dosing (American Pain Society, 1992; 
Weissman, Burchman, Dinndorf, etal., 1992). 


Sedative/ 
hypnotic 
drugs alone 


Barbiturates 
Benzodiazepine 


Analgesic properties not demonstrated. Added 
sedation from sedative/hypnotic drugs limits 
opioid dosing (American Pain Society, 1992). 


Routes of administration Rationale for not recommending 


Intramuscular (IM) 


Painful. Absorption unreliable (American 
Pain Society, 1992). Should not be used for 
children or patients prone to develop dependent 
edema or in patients with thrombocytopenia 
(Weissman, Burchman, Dinndorf, et al., 1992). 


Transnasal 


The only drug approved by the FDA for 
transnasal administration at this time is butor- 
phanol, an agonist-antagonist drug, which 
generally is not recommended. (See opioid 
agonist-antagonists above.) 



73 



Figure 5. Pain management plan 



Pain control plan for 



At home, I will take the following medicines for pain control: 

Medicine How to How How Comments 

take many often 



Medicines that you may take to help treat side effects: 

Side Medicine How How How Comments 

effect to take many often 



Constipation is a very common problem when taking opioid medications. 
When this occurs, do the following: 

□ Increase fluid intake (8 to 1 glasses of fluid) 

□ Exercise regularly 

□ Increase fiber in the diet (bran, fresh fruits, vegetables) 

□ Use a mild laxative, such as milk of magnesia, if no bowel movement in 3 days 

□ Take every day at (time) with a full 

glass of water 

□ Use a glycerin suppository every morning (this may help make a 
bowel movement less painful) 

Non-drug pain control methods: 



Additional instructions: 



Important phone numbers: 

Your doctor Your nurse 

Your pharmacy Emergencies 



Call your doctor or nurse immediately if your pain increases or if you have a new 
pain. Also call your doctor early for refill of pain medicines. Do not let your medi- 
cines get below 3 or 4 days' supply. 

74 



4Nonpharmacologic 
Management: Physical and 
Psychological Modalities 

Recommendations 

31. Cutaneous stimulation techniques, including applications of super- 
ficial heat and cold, massage, pressure or vibration, should be 
offered to alleviate pain associated with muscle tension or muscle 
spasm. (C) 

32. Patients should be encouraged to remain active and to participate 
in self-care when possible. (A) 

33. Clinicians should reposition patients on a scheduled basis during 
long-term bedrest and provide active and passive range-of-motion 
exercises. For a patient in acute pain, exercise should be limited to 
self-administered range of motion. (C) 

34. Prolonged immobilization should be avoided whenever possible to 
prevent joint contracture, muscle atrophy, cardiovascular decondi- 
tioning, and other untoward effects. (B) 

35. Patients who choose to have acupuncture for pain management 
should be encouraged to report new pain problems to their health 
care team before seeking palliation through acupuncture. (Panel 
Consensus) 

36. Psychosocial interventions should be introduced early in the course 
of illness as part of a multimodal approach to pain management. 
They generally should not be used as substitutes for analgesics. (A) 

37. Because of the many misconceptions regarding pain and its treat- 
ment, education about the ability to control pain effectively and 
correction of myths about the use of opioids should be included as 
part of the treatment plan for all patients. (B) 

38. Clinicians should offer patients and families means to contact peer 
support groups. (Panel Consensus) 

39. Pastoral care members should participate in health care team 
meetings that discuss the needs and treatment of patients. They 
should develop information about community resources that 
provide the spiritual care and support of patients and their fami- 
lies. (Panel Consensus) 

75 



Management of Cancer Pain 

Introduction 

Physical and psychosocial therapies can be used concurrently with 
drugs and other modalities to manage pain. These interventions can 
be carried out by professional staff and often by the patient or family 
members. 

Physical Modalities 

Physical modalities include cutaneous stimulation, exercise, immo- 
bilization, transcutaneous electrical nerve stimulation (TENS), and 
acupuncture (Lee, Itoh, Yang, et al., 1990). Their use may decrease 
the need for pain-reducing drugs, but they should not be used as 
substitutes for medication. These modalities should be introduced 
early to treat generalized weakness and deconditioning as well as 
aches and pains associated with periods of inactivity and immobility 
related to cancer diagnosis and therapy. 

Cutaneous Stimulation 



Cutaneous stimulation includes the application of superficial heat 
(thermotherapy) and cold (cryotherapy) (Mayer, 1985). Other meth- 
ods, such as massage, pressure, and vibration, may help patients to 
relax or distract them from their pain. Cutaneous stimulation some- 
times increases pain briefly before pain relief occurs (McCaffery and 
Beebe, 1989). These methods are noninvasive and usually can be 
easily taught to the patient or family caregiver. 

Superficial applications of heat act through conduction or convec- 
tion to increase the blood flow to the skin and superficial organs and 
to decrease the blood flow to inactive tissues such as the underlying 
musculature (Lehmann and de Lateur, 1990). Heat induces vasodila- 
tion, which increases oxygen and nutrient delivery to damaged tissues 
(Whitney, 1989). Heat also decreases joint stiffness by increasing the 
elastic properties of muscles (Vasudevan, Hegmann, Moore, et al., 
1992). Superficial heat can be applied by hot packs, hot water bottles, 
hot and moist compresses, electric heating pads (dry or moist), 
commercially available chemical and gel packs, and immersion in 
water (tub, basin, or whirlpool) (McCaffery and Wolff, 1992). For all 
types of hot packs, care should be taken to wrap them well to prevent 
burns and to discourage patients from lying directly on them. In most 
cases, the protection of one towel between the skin and the heating 
device is sufficient. If the patient has decreased skin sensation, is using 
an electrical heating device, or tends to lie on top of a hot pack, more 
layers of cloth are needed for skin protection and close monitoring of 



76 



Physical and Psychological Modalities 

the skin condition is required. Heat should not be applied to tissue 
that has been exposed to radiation therapy. 

The literature is divided on the use of heat in patients with cancer. 
Superficial heat is commonly used by patients to reduce pain 
(Barbour, McGuire, and Kirchhoff, 1986; Davis, Cortex, and Rubin, 
1990; Donovan and Dillon, 1987; Rhiner, Ferrell, Ferrell, et al., 1993; 
Wilkie, Lovejoy, Dodd, et al., 1988), and some texts recommend heat 
to reduce pain and discomfort (Ferrell, Rhiner, and Ferrell, 1993; 
McCaffery and Wolff, 1992; Vasudevan, Hegmann, Moore, et al., 
1992). Other texts, however, caution against the use of heat because of 
concern that the use of heat over tumor sites will increase tumor 
growth and the metastatic spread of the disease (Lee, Itoh, Yang, et 
al., 1990; Lehmann and de Lateur, 1990; Pfalzer, 1992). Research 
evidence cited in support of this cautionary statement is from a 1940 
study of rats (Hayashi, 1940), as well as several studies of fetal tissue 
cells exposed to high degrees of temperature (Lehmann and de 
Lateur, 1990). 

In view of the lack of research findings that clearly contraindicate 
this use of superficial heat, the panel recommends that it be used as a 
method of pain control in patients with cancer. Modalities to deliver 
deep heat — such as short wave diathermy, microwave diathermy, and 
ultrasound — should be used with caution in patients with active 
cancer; they should not be applied directly over a cancer site 
(Lehmann and de Lateur, 1990). 

Cold therapy, which causes vasoconstriction and local hyperesthe- 
sia, is effective in reducing inflammation, edema soon after an injury, 
burning perineal pain (Evans, Lloyd, and Jack, 1981), and muscle 
spasm (Vasudevan, Hegmann, Moore, et al., 1992), and is recom- 
mended when superficial heat is ineffective in reducing spasm. Ice 
packs, towels soaked in ice water, or commercially prepared chemical 
gel packs can be used. Cold packs should be sealed to prevent drip- 
ping, they should be flexible to conform to body contours, they should 
be applied so as to produce a comfortable and safe intensity of cold, 
and they should be adequately wrapped (e.g., in one layer of towel or 
pillowcase) to prevent skin irritation. The duration of ice application 
is shorter than that of heat, usually lasting less than 15 minutes; 
however, it produces a longer acting effect, provided that the muscle is 
actually cooled (Lehmann and de Lateur, 1990; Michlovitz, 1990). 

Cold should not be applied to tissue that has been damaged by radi- 
ation therapy and is contraindicated for any condition in which vaso- 
constriction increases symptoms, such as in peripheral vascular disease, 
Raynaud's syndrome, or other vascular or connective tissue diseases 
(Lehmann and de Lateur, 1990; Whitney, 1989). In some patients, cool- 
ing painful joints will increase range of motion, but in others, this may 
increase joint stiffness and should therefore be avoided. 

77 



Management of Cancer Pain 

Massage is a comfort measure used to aid relaxation and ease 
general aches and pains, particularly those associated with periods of 
treatment related immobility. Massage may also decrease pain in a 
specific area by increasing superficial circulation (Fairchild, Salerno, 
Wedding, et al., 1986; McCaffery and Wolff, 1992). Common tech- 
niques of massage are stroking, kneading, and rubbing with rhythmic, 
circular, distal-to-proximal motions (Lee, Itoh, Yang, et al., 1990). An 
alcohol-free lotion can be used to reduce friction. The patient should 
be encouraged to choose movements that provide the greatest 
comfort. Massage cannot strengthen debilitated muscles, and it should 
not be used in place of exercise and activity for patients who are able 
to walk. Manual or mechanical vibration can also be used to increase 
superficial circulation. Specific instructions for the use of a variety of 
cutaneous stimulation methods for pain relief are available elsewhere 
(McCaffery and Beebe, 1989). An example of a relaxation technique 
that uses massage, touch, and warmth is included in Attachment C. 

Exercise 

Exercise is important for the treatment of subacute and chronic 
pain because it strengthens weak muscles, mobilizes stiff joints, helps 
restore coordination and balance, enhances patient comfort, and 
provides cardiovascular conditioning (Vasudevan, Hegmann, Moore, 
et al, 1992). Barbour, McGuire, and Kirchhoff (1986) found that some 
patients use position change or exercise as a self-initiated strategy for 
pain relief; of those who used these strategies, 86 percent reported 
pain relief with change of position and 25 percent reported pain relief 
after exercise. Patients should be encouraged to remain active and 
participate in self-care when possible (Kohl, LaPorte and Blair, 1988; 
Kovar, Allegrante, MacKenzie, et al., 1992; Powell, Thompson, 
Caspersen, et al., 1987; Siscovick, LaPorte, and Newman, 1985). 

When patients are unable to maintain function, families should be 
taught a simple routine of range-of-motion exercises and massage to 
minimize discomfort and preserve muscle length and joint function 
during periods of decreased function and immobility (Kisner and 
Colby, 1985). Passive exercises should not be carried out if they 
increase pain. During acute pain, exercise should be limited to self- 
administered range of motion (Lee, Itoh, Yang, et al., 1990). All forms 
of exercise that involve weight bearing should be avoided when patho- 
logic fracture is likely because of tumor invasion. 

Positioning is another simple method to promote comfort and to 
prevent or relieve pain. Clinicians should ensure that patients who are 
bedridden are positioned in correct body alignment, that patients are 
repositioned frequently, that skin condition is monitored, and that 
range-of-motion exercises are provided. Clinicians should educate 

78 



Physical and Psychological Modalities 

ancillary personnel and family caregivers so that they are able to 
perform range of motion exercises correctly and safely position patients. 

Immobilization or restriction of movement is often used to 
manage episodes of acute pain and to stabilize fractures or otherwise 
compromised limbs, joints, or both. When immobility is desired, 
supportive devices such as adjustable elastic or thermoplastic braces can 
be used to maintain optimal body alignment. Joints should not be main- 
tained at their maximal range but in their position of optimal function 
(i.e., wrist at 30° of dorsiflexion with thumb opposed to fingers, ankle at 
90° flexion with 5° to 10° flexion of the knee, etc.) to allow for maximal 
function after an immobilization period (Lee, Itoh, Yang, et al., 1990). 
In patients with bone metastasis, immobilization may be necessary to 
prevent fractures. These patients and their families should be taught 
how to apply orthotic devices properly and how to prevent torsion 
during positioning and turning. Prolonged immobilization should be 
avoided whenever possible to prevent joint contracture, muscle atro- 
phy, cardiovascular de conditioning, and other untoward effects. 

Counterstimulation 



Counterstimulation denotes techniques, such as TENS therapy 
and acupuncture, that are believed to activate endogenous pain- 
modulating pathways by direct stimulation of peripheral nerves 
(Sjolund and Eriksson, 1979). The literature in support of these inter- 
ventions is inconclusive, although some patients report that they 
obtain relief from their use (Avellanosa and West, 1982; Bauer, 1983). 

Transcutaneous Electrical Nerve Stimulation (TENS). TENS 
is a method of applying controlled, low-voltage electrical stimulation 
to large, myelinated peripheral nerve fibers via cutaneous electrodes 
for the purpose of modulating stimulus transmission and relieving 
pain. Research on TENS therapy in patients with cancer is limited to 
single-group studies and case reports (Avellanosa and West, 1982; 
Bauer, 1983). A meta-analysis of studies of TENS therapy in postoper- 
ative patients (Acute Pain Management Guideline Panel, in press) 
found that both TENS and sham TENS significantly reduced pain 
intensity; no significant differences were found between the two for 
either analgesic use or pain intensity. These results suggest that, just 
as with some other interventions, part of the efficacy of TENS can be 
attributed to a placebo effect. Patients with mild pain may benefit 
from a trial of TENS. 

Acupuncture. Acupuncture is a neurostimulatory technique that 
treats pain by the insertion of small, solid needles into the skin at 
varying depths, typically penetrating the underlying musculature. 
There are few controlled studies of its use; recent meta-analyses 
(Patel, Gutzwiller, Paccaud, et al., 1989; ter Riet, Kleijnen, and 

79 



Management of Cancer Pain 

Knipschild, 1990) are inconclusive and do not specify which types of 
pain problems acupuncture can or cannot alleviate. 

Pain can signal disease progression, the emergence of adventitious 
infection, or some significant complication of treatment. Therefore, 
patients who choose to have acupuncture for pain management should 
be encouraged to report new pain problems to their health care team 
before seeking palliation through acupuncture. Maintaining an open 
and accepting relationship will make it easier for the patient and the 
practitioner to discuss negative as well as positive experiences and 
situations where acupuncture might be contraindicated. 

When a patient seeks TENS therapy or acupuncture, clinicians 
should listen for clues that would indicate that the pain is uncon- 
trolled. If the patient is seeking these modalities because of poorly 
managed pain, the clinician, in cooperation with the patient, should 
revise the pain management plan by: 

■ Correcting misconceptions the patient might have concerning the 
use of analgesic drugs, especially the phenomena of addiction and 
tolerance with opioids. 

■ Increasing an analgesic dosage. 

■ Adding an adjuvant drug to manage a specific pain complaint or 
to counteract a side effect. 

■ Prescribing a psychotropic drug to manage coexisting anxiety or 
depression. 

■ Providing training in the use of cognitive-behavioral strategies. 

Controlled studies are needed to test the effectiveness of counter- 
stimulation in the treatment of cancer-related pain. 

Psychosocial Interventions 

Psychosocial interventions are an important part of a multimodal 
approach to pain management. Such interventions do not replace, but 
rather, are used in conjunction with appropriate analgesics for the 
management of pain. When psychosocial interventions are successful 
in relieving pain, clinicians should never conclude that the pain was 
not "real." 

One goal is to help the patient gain a sense of control over the 
pain. A simple rationale underlies such intervention: How people 
think affects how they feel, and changing how they think about pain 
can change their sensitivity to it and their feelings and reactions 
toward it (McGrath, 1990b). 

Psychosocial intervention may use cognitive or behavioral tech- 
niques or both. Focusing on perception and thought, cognitive 

80 



Physical and Psychological Modalities 

techniques are designed to influence how one interprets events and 
bodily sensations. Giving patients information about pain and its 
management and helping patients to think differently about their pain 
are both cognitive techniques. Behavioral techniques, by contrast, are 
directed at helping patients develop skills to cope with pain and help- 
ing them modify their reactions to pain. 

Many patients with cancer are highly motivated to use cognitive- 
behavioral methods, which are often effective not only in controlling 
symptoms, but also in restoring the patient's sense of self-control, 
personal efficacy, and active participation in his/her own care. 

In recommending psychosocial interventions, the clinician should 
consider: 

■ Intensity of pain. 

■ Expected duration of pain. 

■ Patient's mental clarity. 

■ Patient's past experience with the technique. 

■ Patient's physical ability. 

■ Patient's desire to employ active or passive techniques. 

Psychosocial interventions should be introduced early in the 
course of illness so that patients can learn and practice these strategies 
while they have sufficient strength and energy. When introduced early, 
they are more likely to succeed, which fosters the patient's motivation 
to continue using them. Patients and their families should be given 
information that describes strategies commonly used to manage pain 
and anxiety and encouraged to try several strategies, then select one 
or more to use regularly when they experience pain. 

As with other modalities, psychosocial interventions can require 
different levels of training and expertise on the part of clinicians. The 
interventions discussed here, however, can be performed by most clin- 
icians. In addition to these interventions, some patients will benefit 
from short-term psychotherapy (see Chapter 7). 

Relaxation and Imagery 



Relaxation techniques and imagery are used to achieve a state of 
mental and physical relaxation. Mental relaxation means alleviation of 
anxiety; physical relaxation means reduction in skeletal muscle 
tension. Relaxation techniques include simple focused-breathing exer- 
cises, progressive muscle relaxation, meditation, and music-assisted 
relaxation (McCaffery and Beebe, 1989) (Attachment C). Simple 
relaxation techniques should be used for episodes of brief pain, e.g., 

81 



Management of Cancer Pain 

during procedures, as well as when the patient's ability to concentrate 
is compromised by severe pain, a high level of anxiety, or fatigue. 

Pleasant mental images can be used to aid relaxation. For exam- 
ple, patients might be encouraged to visualize a peaceful scene, such 
as waves softly hitting the beach, or to take slow, deep breaths as they 
visualize pain leaving the body. Both pleasant imagery and progressive 
muscle relaxation have been shown to decrease self-reported pain 
intensity and pain distress (Graff am and Johnson, 1987). 

Relaxation techniques are most helpful when combined with 
imagery, especially when the image is individualized to the patient's 
needs or preferences (Syrjala, in press). The advantages include: 

■ They are easy to learn. 

■ No special equipment is required. 

■ Staff do not require extensive training. 

■ They are often readily accepted by patients (Hendler and Redd, 
1986; Syrjala, 1990). 

Tapes and other resources are available for teaching relaxation 
(McCaffery and Beebe, 1989; Syrjala, 1990). 



Distraction and Refraining. 



Distraction is the strategy of focusing one's attention on stimuli 
other than pain or the accompanying negative emotions (McCaffery 
and Beebe, 1989; McCaul and Malott, 1984). Distractions may be 
internal, for example, counting, singing mentally to one's self, praying, 
or making self-statements such as "I can cope," or external, for exam- 
ple, listening to music as an aid to relaxation (Beck, 1991; Munro and 
Mount, 1978), watching television, talking to family and friends, or 
listening to someone read. Distraction exercises often include repeti- 
tive actions or cognitive activity, such as rhythmic massage or the use 
of a visual focal point. Distraction may be used alone to manage mild 
pain or as an adjunct to analgesic drugs to manage brief episodes of 
severe pain, such as procedure-related pain. 

A related technique, reframing or cognitive reappraisal, teaches 
patients to monitor and evaluate negative thoughts and images and 
replace them with more positive ones. For example, patients who are 
preoccupied with a fear of pain can be encouraged to use positive self- 
statements to facilitate coping (e.g., "I've had similar pain and it's 
gotten better"). Reframing can add to patients' feelings of control 
over their situations (see Attachment C). 

82 



Physical and Psychological Modalities 

Patient Education 

Patient education entails giving patients and families accurate and 
understandable information about pain, pain assessment, and the use 
of drugs and other methods of pain relief, emphasizing that almost all 
pain can be effectively managed. It should also address major barriers 
to effective pain management, namely, patients' reluctance to talk 
about their pain with their care providers, their unfounded fears about 
becoming addicted to opioids, and their fears that the pain cannot be 
effectively controlled without unacceptable consequences. Patient 
education should address other misconceptions, such as the thought 
that pain medication should be saved for when pain is severe, or else it 
might not be effective (Ward, Goldberg, Miller-McCauley, et al., 
1993). Some believe that analgesics might produce unacceptable side 
effects or that choices might have to be made between treating the 
disease or treating the pain. 

A goal of patient education is to involve patients in their pain 
management: one of the most important steps toward improved 
control of cancer pain is better understanding by patients of the 
nature of the pain, its treatment, and the role that they need to play in 
pain control. Patients should be encouraged to report pain as active 
participants in their own care. To improve their understanding of drug 
therapy and its effects, patients should be told that: 

■ The use of opioid analgesics will not lead to addiction. 

■ Tolerance to opioid analgesics can be dealt with by upward dosage 
adjustments. 

Many patients worry that, if they complain of pain, their health 
care providers might not think of them as "good" patients (Ward, 
Goldberg, Miller-McCauley, et al., 1993). Because of these concerns, 
some patients who are taking opioids and have been told to take them 
regularly may take them only when their pain is severe. Patients 
should be taught that the prevention of pain by the use of regularly 
scheduled analgesics is desirable. Because of the many misconceptions 
regarding pain and its treatment, education about the ability to 
control pain effectively and correction of myths about the use of 
opioids should be included as part of the treatment plan. 

Table 16 specifies some of the major topics of a patient education 
program. The literature indicates that, to have the desired effect, infor- 
mation should be presented more than once and, because patients seek 
information from multiple sources, in more than one way. 

Because uncertainty increases distress and threatens the percep- 
tion of ability to cope, informing patients about what is going to 
happen to them can help them think about a situation differently and 

83 



Management of Cancer Pain 

Table 1 6. Patient education program content 

General overview 

Pain can be relieved. 

Defining pain. 

Understanding the causes of pain. 

Pain assessment and use of pain-rating scales to 
communicate pain. 

Talking to doctors and nurses about pain. 

Using a preventive approach to pain control. 

Pharmacologic management 

Overview of drug management of pain. 

Overcoming fears of addiction and drug tolerance. 

Understanding drug tolerance. 

Understanding respiratory depression. 

Controlling common side effects of drugs (e.g., nausea and constipation). 

Nonpharmacologic management 

Importance of nonpharmacologic interventions. 

Use of nonpharmacologic modalities as adjuncts to analgesics. 

Review of previous experience with nonpharmacologic modalities. 

Peer support groups and pastoral counseling. 

Demonstration of heat, cold, massage, relaxation, imagery, and distraction. 

Source: Ferrell, Rhiner, and Ferrell, 1993. 



feel less helpless (Mishel, 1984). Research has shown that patients 
who receive medication-related education have a higher rate of 
compliance with analgesic prescriptions, fewer concerns about taking 
opioid analgesics, and lower pain levels than do patients not given 
such information (Rimer, Levy, Keintz, et al., 1987). Other research 
has demonstrated that informing patients about possible side effects 
of therapy will not increase the occurrence of side effects or have 
other adverse effects (Howland, Baker, and Poe, 1990; Wilson, 1981). 
After the clinician has told patients that they are expected to take 
an active role in their pain management and has reassured them that 
pain relief is an important goal, then patients should be able to use 
clinicians as sources of information and reassurance about pain 
control. Information presented orally to patients should be supple- 
mented with written material (Table 17). Additional information is 
included in a discussion of discharge planning in Chapter 3. 

84 



Physical and Psychological Modalities 
Table 1 7. Sources of information for patients and their families 



Cancer Pain Can Be Relieved. 

Wisconsin Cancer Pain Initiative; 1988, p. 10. 1 

This booklet gives clear and concise answers to 21 questions frequently asked by people with 
cancer pain. Topics include communicating pain to health providers, analgesics available to 
relieve pain, and management of side effects associated with opioid analgesics. 

Children's Cancer Pain Can Be Relieved. 
Wisconsin Cancer Pain Initiative; 1989, p. 12. 1 

This booklet is written for parents of children who have cancer and discusses many issues 
that confront children in pain and their families. A question-and-answer format is used to 
explain the assessment of pain in infants and children, the use of analgesics, and the 
management of side effects. Resources for families of children with cancer also are included. 

Jeff Asks About Cancer Pain. 

Wisconsin Cancer Pain Initiative; 1990, p. 12. 1 

This booklet addresses accurately and candidly the needs of adolescents who have cancer 
pain. It includes myths regarding addiction, methods for relieving side effects of opioids, and 
instructions for taking opioid analgesics during school hours. Adolescents will appreciate the 
language and style. 

Questions and Answers About Pain Control: A Guide for People With Cancer and Their Fami- 
lies. American Cancer Society and the National Cancer Institute; 1992, p. 76. 2 

This book provides in-depth and current information in an easy-to-understand, question-and- 
answer format. Information is included on pain assessment, nonprescription and prescription 
medications, and nondrug interventions such as relaxation, imagery, and applications of 
superficial heat and cold. Common fears related to opioid analgesics (i.e., safety, addiction) 
are discussed, and tips for managing side effects of opioid analgesics are provided. 

Facing Forward: A Guide for Cancer Survivors. 

U.S. Department of Health and Human Services, Public Health Service, National Institutes of 

Health, National Cancer Institute, July 1990. NIH Publication No. 90-2424, p. 43. 2 

This booklet was developed to give cancer survivors practical ideas to help cope with 
common concerns. The topics covered are: continuing to care for your health; taking care of 
your feelings; managing insurance issues; and earning a living. Experiences of other cancer 
survivors are included, as well as facts, practical tips, options for taking control of your situa- 
tion, and other resources that may be useful. 

Teamwork: The Cancer Patient's Guide to Talking With Your Doctor. National Coalition for 
Cancer Survivorship, 1991, p. 32. 3 

This booklet is written by cancer survivors and doctors to help other patients with cancer 
learn how to communicate effectively with their doctors. Topics include what to tell your 
doctor about yourself; what doctors wish their patients knew; understanding (and remember- 
ing!) what the doctor says; and key questions to ask your doctor throughout the process, from 
before the diagnosis through all stages of treatment. 

Available from the Wisconsin Cancer Pain Initiative, 3675 Medical Sciences Center, 

1300 University Avenue, Madison, Wl 53706. Phone: (608) 262-0978. 

2 Available from local units and chapters of the American Cancer Society, Phone: 1-800-ACS- 

2345. Also available from the National Cancer Institute. Phone: 1-800-4-CANCER. 

3 Available from the National Coalition for Cancer Survivorship, 1010 Wayne Avenue, 5th Floor, 

Silver Spring, MD 20910. Phone: (301) 650-8868. 

Source: Adapted with permission from Paice, 1 990. 



85 



Management of Cancer Pain 

Psychotherapy and Structured Support. 



Some patients benefit from short-term psychotherapy or more 
complex cognitive-behavioral interventions provided by a psychiatrist, 
clinical psychologist, psychiatric nurse, or psychiatric social worker. 
Short-term supportive psychotherapy based on a crisis intervention 
model can provide emotional support, continuity, and information 
while helping the patient adapt to the crisis. The therapist emphasizes 
the patient's past strengths, supports the patient's use of previously 
successful coping strategies, and teaches new coping skills. Studies 
have shown that patients with cancer who receive active, structured 
psychological support report less pain and live longer (Fawzy, 
Cousins, Fawzy, et al., 1990; Spiegel and Bloom, 1983; Spiegel, Bloom, 
Kraemer, et al., 1989). Psychotherapy should be offered to patients 
whose pain is particularly difficult to manage (e.g., substance abusers), 
those who develop symptoms of clinical depression or another adjust- 
ment disorder, and those with a history of psychiatric illness. 

Hypnosis 

The hypnotic trance is a state of heightened awareness and 
focused concentration that can be used to manipulate the perception 
of pain and has been effective in the treatment of cancer-related pain 
(Reeves, Redd, Storm, et al., 1983; Spiegel and Bloom, 1983; Syrjala, 
Cummings, and Donaldson, 1992). It should only be administered by 
specially trained professionals. 

Peer Support Groups 



Programs of self-help and mutual support of patients with cancer 
have been available since the 1940s, when the American Cancer Soci- 
ety (ACS) established visitor programs to offer practical help for 
patients at home (Mastrovito, Moynihan, and Parsonnet, 1989). Some, 
such as the National Coalition for Cancer Survivorship and many of 
their local chapters, enroll survivors of any type of cancer and their 
relatives. Others target specific cancers; these include the Interna- 
tional Association of Laryngectomees, the United Ostomy Associa- 
tion, and the ACS's Reach to Recovery program for breast surgery 
patients. Many of the peer support groups work closely with health 
care teams who refer patients to them. 

The experience and empathy of people who have experienced a 
disease can provide credible support to others with the same disease 
or problem and can help new patients learn to cope more effectively 
(Mantell, Alexander, and Kleiman, 1976). Support networks can also 
help patients to maintain social identity and provide emotional 

86 



Physical and Psychological Modalities 
Table 18. How to find local support groups 

Call the local unit of the American Cancer Society; see the phone book in the 
business white pages. 

Contact the National Coalition for Cancer Survivorship: 
1 01 Wayne Avenue, 5th Floor 
Silver Spring, MD 20910 
(301)650-8868 

Call the National Cancer Information Service, 1-800-4-CANCER. 

Call the State self-help clearinghouse; the American Self-Help Clearinghouse at 
(201)642-7101 has information on State clearinghouses. 

Contact the social service department of cancer treatment centers, an oncology 
social worker, or cancer counselor. 

Call the local mental health department. 

Check local newspapers for weekly listings. 

Call the local United Way office or other community fund offices. 



support, material aid, and access to information (Walker, MacBride, 
and Vachon, 1977). Because of the benefits provided by these groups, 
clinicians should know which are active in their area and provide this 
information to patients who wish to join them. Table 18 provides 
suggestions on how to find a support group. 



Pastoral Counseling. 



Having cancer and pain frequently raises issues of spirituality for 
patients and their families, both of whom may be helped by pastoral 
counseling. The experience of pain can often lead patients to fear 
abandonment and to question meaning and the possibility of hope. 
Many religions address these concerns and offer an important dimen- 
sion in a multidisciplinary approach to pain management. Thus: 

■ Ecumenical pastoral care should be made available. 

■ Pastoral care members should participate in health care team 
meetings that discuss the needs and treatment of patients. 

■ Pastoral care members should develop information about 
community resources that provide spiritual care and support. 



87 



5 



Nonpharmacologic Interventions: 
Invasive Therapies 



Recommendations 

40. With rare exception, noninvasive treatments should precede inva- 
sive palliative approaches. (Panel Consensus) 

41. Indications for palliative radiation therapy include treatment of 
symptomatic metastases in sites where tumor infiltration has 
caused pain, obstruction, bleeding, or compression. (B) 

42. Radiopharmaceuticals emitting a (3 -particle should be used for the 
pain of bone metastases only when bone scintigraphy shows a 
lesion. (A) 

43. Radiation tolerance of adjacent normal tissues should be consid- 
ered in the design of treatment portals and the prescription of 
teletherapy or radiopharmaceutical dose. (A) 

44. The desired dosage of radiation should be administered in the 
fewest fractions possible to promote patient comfort during and 
after treatment. (Panel Consensus) 

45. Neurolytic blockade of peripheral nerves should be reserved with 
rare exception for instances in which other therapies (palliative 
radiation, TENS, pharmacotherapy) are ineffective, poorly toler- 
ated, or clinically inappropriate. (Panel Consensus) 

46. Clinicians should: 

■ Assess thoroughly each patient's pain mechanism in order to 
apply the most appropriate nerve block. 

■ Screen patients for coexistent medical conditions, ability to 
understand risks of the proposed procedure, and ability to 
cooperate during the procedure. 

■ Consider a block only if the person planning to do it is experi- 
enced and skillful, is prepared to deal with its immediate 
effects and side effects, and is able to provide follow-up assess- 
ment and treatment. 

■ Use radiographic control for blocks when ease and safety 
depend on precise anatomic guidance. (Panel Consensus) 

47. When a patient is painfree after neurolysis, opioids should not be 
stopped abruptly, lest a withdrawal syndrome be provoked. (B) 

89 



Management of Cancer Pain 

48. The oncologic surgeon should be familiar with the interactions of 
chemotherapy, radiation therapy, and surgical interventions so that 
iatrogenic complications may be avoided or anticipated. 

(Panel Consensus) 

49. The surgeon should recognize and treat characteristic pain syn- 
dromes that follow specific surgical procedures. (Panel Consensus) 

Introduction 

Invasive nonpharmacologic interventions complement behavioral, 
physical, and drug therapies in a substantial minority of patients in 
whom these therapies alone do not control pain (see Figure 3). With 
rare exception, noninvasive analgesic approaches should precede inva- 
sive palliative approaches. Although radiotherapy and surgery can cure 
primary disease, they are discussed here in relation to pain relief only. 
Surgical procedures are useful in selected patients to debulk tumors 
and hence reduce symptoms of obstruction or compression. Anesthetic 
and neurosurgical methods can be used to ablate pain pathways or 
implant devices for drug delivery or electrical stimulation of neural 
structures. For any invasive therapy, the risks, availability of expertise 
and suitable support systems, and cost should be considered in addition 
to the apparent necessity or medical indication. 

Radiation Therapy 

Radiation therapy can relieve metastatic pain as well as symptoms 
from local extension of primary disease (Greenwald, Bonica, and 
Bergner, 1987). Over one-third of the practice of radiation therapy is 
palliative (Arcangeli, Micheli, Arcangeli, et al., 1989). The intent of 
any palliative treatment is to relieve pain quickly and maintain symp- 
tom control for the duration of the patient's life. Treatment is therefore 
tailored to the patient's clinical condition and overall prognosis 
(Lawton and Maher, 1991; Maher, Coia, Duncan, et al., 1992). Radia- 
tion therapy is complementary to analgesic drug therapies and may 
enhance their effectiveness because it directly targets the cause of pain. 

In general, the larger the daily dose of radiation, the lower the 
total dose that can be administered because of limits to normal tissue 
tolerance. Proportionately more tumor cells are killed when the daily 
radiation dose is larger. A balance is required between the killing of 
tumor cells and the adverse radiation effects on normal tissues, which 
are largely a function of the daily dose. A number of different sched- 
ules have been developed that take into account specific tumor char- 
acteristics and the tolerance of normal tissues. The literature is 
divided regarding the optimal radiation schedule to achieve tumor 

90 



Invasive Therapies 

regression (Hall, 1993; Thames, Withers, Peters, et al., 1982) and 
disease palliation (Price, Hoskin, Easton, et al., 1986) at either 
primary or metastatic sites. Generally, however, radiation treatment is 
planned in relation to clinical status. 

The toxicity of radiation is determined by the structures included 
within the radiation portal, the dose per fraction, the total dose, and 
the radiation sensitivity of the tissues involved. The desired dosage of 
radiation should be administered in the fewest fractions possible to 
promote patient comfort during and after treatment. Radiation side 
effects are restricted to the radiation portal and can be classified as 
either acute, occurring during or immediately after the course of radi- 
ation therapy, or late, occurring months to years later. Acute radiation 
effects are more prominent with radiation schedules that deliver high 
total doses of radiation with small daily fractions; they generally begin 
at the end of the second week of therapy (Hall, 1993). Acute radiation 
effects, occurring primarily at skin and mucosal surfaces, usually 
consist of an inflammatory response such as skin erythema or pigmen- 
tation, or as mucositis. Acute reactions, however, are generally mild 
during palliative therapy schedules, which deliver high daily radiation 
doses over 1 to 2 weeks. Late radiation effects may arise without any 
preceding acute reactions. Fibrosis is the most common type of late 
radiation injury and can be observed in many types of tissue, including 
skin. Late effects are most prominent in tissues with limited regenera- 
tive capacity such as brain, peripheral nerves, and lungs. Because of 
the limited duration of patient survival, however, late effects are 
seldom seen after palliative radiotherapy. 

Bone Metastases 

Most patients referred for palliation of metastatic bone pain have 
primary tumors of the highest overall incidence: breast, prostate, or 
lung. Other neoplasms involving bone, such as myeloma, also respond 
to radiation. Regular followup should be provided to offer treatment 
of new symptoms or the use of other palliative techniques such as 
radiopharmaceuticals. 

Plain radiographs are useful in detecting lytic or blastic lesions 
from bone metastases. Bone scintigraphy, however, is more sensitive 
than skeletal radiography for the detection of most bone metastases. 
Although 73 percent of patients in one series were asymptomatic 
when skeletal metastases were discovered by scintigraphy, 66 percent 
of these symptom-free patients ultimately experienced moderate to 
severe bone pain (Sherry, Greco, Johnson, et al., 1986a). In patients 
who experience bone pain and have normal bone scans, MRI may be 
a helpful diagnostic tool. 

91 



Management of Cancer Pain 

Indications for the radiation of bone metastases include pain relief 
and the prevention or promotion of healing of pathologic fractures. 
Spinal cord compression associated with vertebral collapse due to 
bony or epidural metastases requires emergent radiation therapy, 
sometimes in coordination with surgical intervention to preserve 
neurologic integrity (Bates, 1992). Orthopedic complications, includ- 
ing pathologic fracture and spinal cord compression, have been 
reported in 36 percent of breast cancer patients with skeletal metas- 
tases (Sherry, Greco, Johnson, et al., 1986b). Lytic lesions that are 2.5 
cm or larger in weight-bearing bones or that cause a more than 50 
percent loss of cortical bone place patients at high risk for pathologic 
fracture (Bates, 1992); patients with such lesions may benefit from 
prophylactic surgical fixation in conjunction with adjuvant irradiation. 

Pain Relief With Localized Radiation Therapy. Radiation is 
commonly administered to a localized bone metastasis. An analysis of 
therapeutic results is complicated by variation in the location and 
extent of bone metastases, primary histology, individual differences 
(including patients' underlying medical conditions), and co-adminis- 
tered treatments. Concurrent analgesic use is frequently a confound- 
ing, poorly quantified variable in many accounts of pain control 
during local radiation of a metastasis. Most retrospective and prospec- 
tive studies report that 75 percent or more of patients obtain relief 
from pain and that about half of those who achieve relief become 
pain-free (Nielsen, Munro, and Tannock, 1991). However, selection 
bias cannot be excluded; valid and reliable pain assessment instru- 
ments were not commonly used. 

The literature is divided on appropriate fractionation (Blitzer, 
1985; Hoskin, 1988; Tong, Gillick, and Hendrickson, 1982). Protracted 
regimens of more than 10 treatments may be more appropriate for 
patients with life expectancies of longer than 6 months to reduce 
potential late radiation effects or acute effects such as nausea if critical 
structures such as the stomach have to be included in the radiation 
field. For patients with a more limited life expectancy, radiation can be 
administered in fewer fractions, depending on the patient's clinical 
status (Lawton and Maher, 1991; Maher, Coia, Duncan, et al., 1992). 
These later regimens result in effective palliation in over 70 percent of 
patients at 3-months' followup, with negligible complications when 
radiation portals are localized (Arcangeli, Micheli, Arcangeli, et al., 
1989; Bates, Yarnold, Blitzer, et al., 1992; Blitzer, 1985; Tong, Gillick, 
and Hendrickson, 1982). 

Wide-Field Radiation Therapy. Hemibody irradiation, which can 
treat multiple disease sites, is particularly appropriate for diffuse bone 
pain. A single large fraction of 6 Gy to 8 Gy is administered to one half 
of the body. If necessary, the other half can be treated after a 3-week 
interval to allow for bone marrow recovery. With antiemetics and 

92 



Invasive Therapies 

partial shielding to reduce lung exposure, toxicity occurs in fewer than 
10 percent of patients, and 50 percent experience stabilization of disease 
at 1-year followup (Poulter, Cosmatos, Rubin, et al., 1992). Salazar, 
Rubin, Hendrickson, et al. (1986) reported that palliation was achieved 
in 73 percent of patients treated with hemibody irradiation, and pain 
recurrence was lower than that reported in an earlier uncontrolled 
study of the palliative effects of local radiotherapy (Tong, Gillick, and 
Hendrickson, 1982). This analysis is consistent with other reported 
studies of hemibody irradiation in which 50 percent of patients report 
at least partial pain relief within 48 hours of treatment with an eventual 
total response rate of 55 to 100 percent (Kuban, Schellhammer, and 
el-Mahdi, 1991; Salazar, Rubin, Hendrickson, et al., 1986). 

Radiopharmaceuticals. Several radiopharmaceuticals have been 
used therapeutically. Iodine-131, used for the treatment of multiple 
bone metastases from thyroid cancer, results in bone scan evidence of 
response in 53 percent of patients (Maxon and Smith, 1990). Phospho- 
rus-32-orthophosphate has provided partial or complete relief of pain 
in about 80 percent of patients with bone metastases from breast and 
prostate carcinoma (Silberstein, Elgazzar, and Kapilivsky, 1992). In an 
analysis of 18 published studies, strontium-89 was found to provide 
partial to complete pain relief for 65 percent (Silberstein, unpublished 
manuscript). For example, Silberstein and Williams (1985) reported a 
palliative response of 51 percent of patients, and Robinson, Spicer, 
Preston, et al. (1987) reported 80 to 89 percent palliative response. In 
these studies, analgesic use and activities of daily living were used as 
measures of palliation. Myelosuppression, manifested by approxi- 
mately a 30 to 50 percent decline in leukocyte and platelet levels 
within 4 to 6 weeks, generally occurs in patients with either extensive 
disease or pretreatment peripheral cytopenia (Lewington, McEwan, 
Ackery, et al., 1991). Rhenium-186 and samarium-153 phosphonate 
chelates have demonstrated 65 to 80 percent efficacy in international 
clinical trials, with FDA approval pending (Maxon, Schroder, Thomas, 
et al., 1990; Turner, Claringbold, Hetherington, et al., 1989). These p- 
emitting radiopharmaceuticals, which require only a single intra- 
venous injection, are used to relieve pain from widespread, osteoblas- 
tic skeletal metastases visualized with bone scintigraphy. If pain 
recurs, 50 percent of patients will respond to a second administration. 

Plexopathy 

Painful nerve compression or infiltration by a malignant tumor 
can sometimes be alleviated by radiation therapy. These primary 
tumors often require fractionated radiation therapy over 5 to 7 weeks 
in an attempt to secure local or regional control of the disease. Dosage 
is limited by the proximity of the tumor to radiosensitive structures, 

93 



Management of Cancer Pain 

such as the spinal cord. Peripheral nerves, however, can tolerate 
higher doses. 

Other Therapeutic Applications 



Palliative radiation can be administered to any location of sympto- 
matic primary or metastatic disease. Aggressive, sometimes protracted 
multimodality therapy may be given to patients with certain primary 
tumors, such as soft tissue sarcomas and carcinomas of the breast, lung, 
and rectum, to relieve both symptoms and to achieve control of 
advanced disease. Palliative radiation may also be given to metastatic 
lesions involving the brain, eye, skin, and soft tissue. Localized radia- 
tion may be used to treat lymph node involvement causing symptoms 
due to pressure on adjacent nerve roots and blood vessels. Intra- 
abdominal tumors may infiltrate the retroperitoneum and adjacent 
nerve roots or may cause local symptoms such as bowel obstruction. 
Although limited by the tolerance of the bowel to radiation, some 
tumor regression and symptomatic relief may be accomplished through 
fractionated radiation. Because the radiation tolerance of normal liver 
or kidney is even lower than that of bowel, treatment of pain due to 
capsular distention of either organ is rarely undertaken. Radiotherapy 
is generally not administered in these cases unless a trial of analgesic 
therapy and, when appropriate, chemotherapy has been unsuccessful. 
Symptomatic bleeding from endobronchial, cervical, and bladder 
tumors can often be stopped by external beam irradiation. 

Brachytherapy 

Brachytherapy involves the placement of a radioactive source 
within tissue to deliver localized radiation and is frequently applied to 
treat recurrent disease in an area previously treated by external beam 
radiation. Advantages include the sparing of critical structures close to 
the tumor, and brevity of treatment (hours to days). Difficulties 
primarily involve anatomic constraints on implant placement. 
Common applications include the endoluminal treatment of recurrent 
endobronchial and bile duct tumors, the intracavitary treatment of 
cervical and endometrial cancer, and interstitial implants in unre- 
sectable tumors with catheters or radioactive seeds. Occasionally, 
hyperthermia will be combined with either brachytherapy or external 
beam irradiation to relieve pain and other symptoms of recurrent 
disease originating from head and neck or breast cancers. 



94 



Invasive Therapies 

Anesthetic Techniques 

Nerve Blocks 

The possibility of controlling otherwise intractable pain by the 
relatively brief application of a local anesthetic or neurolytic agent 
makes neural blockade an attractive approach in selected patients. 
Published estimates of the percentage of all patients with cancer pain 
for whom nerve block procedures may appropriately be considered 
vary greatly. Variability in this estimate reflects evolution of the effec- 
tiveness of noninvasive therapies, interinstitutional differences in 
availability of clinicians with the necessary expertise, and access to 
alternative options such as spinal opioid therapy or neurosurgery 
(Bonica, Buckley, Moricca, et al., 1990). Allowing for vagueness in 
methods of arriving at published estimates, lack of uniformity in clini- 
cal conditions treated by neural blockade, and in reported clinical 
outcomes, it still appears that some 50 to 80 percent of patients who 
receive nerve blocks for cancer pain may benefit (Cousins and Briden- 
baugh, 1987; Patt, 1993; Raj, 1992) (Table 19). 

Local anesthetic such as lidocaine or bupivacaine is typically 
applied at an anatomically defined site to provide diagnostic informa- 
tion (e.g., whether the pain is somatic or visceral; whether it has a 
sympathetic mechanism). Prognostic injection assesses side effects such 
as hypotension and subjective sensations, including pain relief or 
unpleasant numbness, likely to result from a planned neurodestructive 
procedure. Although the lack of a desirable result from local anesthetic 
injection after proper needle placement generally predicts the failure 
of a neurolytic block, a promising result after local anesthetic injection 
does not guarantee the success of subsequent chemical destruction. 

Therapeutic injections of a local anesthetic may provide relief that 
outlasts its pharmacologic action. Prolonged benefit may follow 

Table 19. Nerve blocks 

Purposes of Nerve Blocks 

Diagnostic: to determine source of pain (e.g., somatic nerve versus 

sympathetic pathways). 

Therapeutic: to treat painful conditions that respond to nerve blocks 

(e.g., celiac blocks for pain of pancreatic cancer). 

Prognostic: to predict outcome of permanent interventions such as 

infusions, neurolysis, and rhizotomy. 

Preemptive: to prevent painful sequelae of procedures that may cause 

phantom limb or causalgia. 



95 



Management of Cancer Pain 

injection of trigger points for myofascial pain — a procedure sufficiently 
simple, safe, and efficacious that it can be accomplished by many 
primary care providers. The injection of an anti-inflammatory corticoid 
with a local anesthetic into the spinal space or around nerve roots can 
reduce edema and irritation produced by tumor compression and 
provide analgesia for days to weeks. One or more cervical or lumbar 
sympathetic blocks may result in prolonged relief in patients whose 
cancer-related pain is sympathetically maintained. Sympathetic block 
performed during acute herpes zoster infection can immediately 
decrease pain, hasten resolution, and avert the development of posther- 
petic neuralgia, and should be considered as preemptive therapy for this 
debilitating sequel (Ferrer, 1989). The simpler technique of subcuta- 
neous infiltration with local anesthetic and corticoid has also been 
reported to provide symptomatic relief for herpes zoster. When single 
sympathetic blocks produce only transient benefit, the placement of a 
catheter at the sympathetic ganglion (or the corresponding intraspinal 
segments or interpleural space) to enable continuous sympathetic 
blockade for days to weeks may produce sustained benefit. 

Patient selection and timing of neural destruction for pain relief 
are based on the exhaustion of more conservative modalities, a lack of 
available, clinically superior options, and the availability of capable 
physician and support systems after the procedure. Nondestructive 
analgesic infusion techniques can preempt the need for neurolytic 
procedures. Therapeutic choices depend on patient and family 
preferences and the clinical judgment of their health care providers 
(Verrill, 1990). 

Peripheral nerve destruction can be accomplished by the injection 
of ethanol, phenol, or other neurolytic agents at sites where a previous 
test injection of local anesthetic has produced pain relief. Whereas 
phenol induces warmth and then numbness, alcohol produces intense 
transient burning after injection and hence should be immediately 
preceded by local anesthetic injection. Small volumes of alcohol or 
phenol may be injected intrathecally to destroy nerve root function in a 
localized distribution. Approximately 60 percent of patients treated 
with intraspinal alcohol or phenol experience complete or near- 
complete relief of pain until death (Rodriquez-Bigas, Petrelli, Herrera, 
et al., 1991). When a patient is painfree after neurolysis, opioids should 
not be stopped abruptly, lest a withdrawal syndrome be provoked. 
Complications including paresis, paralysis, and bowel or bladder 
dysfunction affect 0.5 to 2 percent of patients treated with intraspinal 
alcohol or phenol (Gerbershagen, 1981). An epidural injection of 
phenol (or alcohol, according to some reports) can accomplish the 
same goal; however, the targeting of the injectate is less precise, the 
neurolytic effects take place over a more diffuse area than that affected 

96 



Invasive Therapies 

by the intrathecal route, and the technique is less well established than 
intrathecal injection (Salmon, Finch, Lovegrove, et al., 1992). 

Neurolytic sympathetic blockade is useful to relieve pain in the 
arm, head and neck (stellate ganglion), or leg (lumbar sympathetic 
block), as well as to interrupt the visceral afferent pain pathways 
mediating pain in the pancreas and other upper abdominal organs 
(celiac block) or in the pelvis (hypogastric block). Side effects of celiac 
block include transient hypotension and diarrhea; complications (less 
likely with radiologic guidance) include paraplegia or less severe 
radicular weakness or numbness, intrarenal injection and damage, 
retroperitoneal hematoma, and failure of ejaculation (Ischia, Ischia, 
Polati, et al., 1992; van Dongen and Crul, 1991). Four-fifths or more of 
patients with pancreatic or other abdominal cancers derive pain relief 
from celiac block, usually lasting until death (Brown, Bulley, and 
Quiel, 1987; Eisenberg, Carr, and Chalmers, unpublished manuscript; 
Mercandante, 1993). Even when relief is incomplete, patients may 
appreciate the ability to lower their opioid dosage and by doing so 
reduce drowsiness and constipation. It thus appears reasonable to 
consider early celiac neurolytic block for patients with a short life 
expectancy and pain from pancreatic cancer (Mercadante, 1993). A 
recently reported technique for refractory chest wall tumor pain is 
interpleural blockade, which uses long-term local anesthetic infusion 
or single-dose phenol (Lema, Myers, de Leon-Casasola, et al., 1992). 

Neurolytic blockade of peripheral nerves should be reserved for 
instances in which other therapies (palliative irradiation, TENS, phar- 
macotherapy) are ineffective, poorly tolerated, or clinically inappropri- 
ate. Suitable targets for this approach include intercostal nerves at the 
site of painful tumor, after maximal doses of radiation and systemic 
analgesics, or nerves of the head and neck (e.g., gasserian ganglion). 
Pain recurrence due to neuritis is common because an alcohol-damaged 
nerve regenerates over weeks to months. If the mechanism of pain is 
partial or complete denervation, this will not be corrected (and may 
potentially be worsened) by further chemical damage to the nerve. 

Pain that is diffuse (e.g., from multiple bony metastases) may 
respond to chemical ablation of the pituitary, which is accomplished 
by alcohol administered through a needle advanced transnasally until 
its tip rests in the pituitary fossa (see also Neurosurgery, below). Pain 
relief by this intervention may be rapid and striking, while ascending 
nociceptive pathways remain unharmed. Pain relief has been reported 
in about two-thirds of patients, whether or not the primary tumor is 
hormone dependent (Takeda, Fujii, Uki, et al., 1983). Complications 
include headache, persistent leakage of CSF, coma, and cranial nerve 
palsies, all of which occur at a frequency of 5 percent or less (Cook, 
Campbell, and Puddy, 1984). Diabetes insipidus is a predictable side 
effect of complete pituitary ablation. 

97 



Management of Cancer Pain 

Technical aspects of the above procedures are beyond the scope of 
this guideline and are well described in a number of recent mono- 
graphs (Abram, 1989; Charlton, 1986; Cousins and Bridenbaugh, 1987; 
Swerdlow, 1987). Complications associated with local anesthetic nerve 
blocks, catheter implants, neurostimulator implants, thermal abla- 
tions, and neurolytic injection have been reported (Cousins and 
Bridenbaugh, 1987; Melzack and Wall, 1989; Raj, 1992). Serious side 
effects including hemorrhage, infection, unexpected nerve damage, 
pneumothorax, and cardiorespiratory arrest are rare but nonetheless 
mandate resuscitative skills and close short-term followup. 

Because of the appeal of nerve blocks for use in intractable pain 
and their potential for harm as well as benefit, clinicians should: 

■ Assess thoroughly each patient's pain mechanism, in order to 
apply the most appropriate block. 

■ Screen patients according to coexistent medical conditions (e.g., 
coagulopathy); ability to understand risks of the proposed proce- 
dure (e.g., paresis or incontinence); and ability to cooperate 
during the procedure (e.g., not move). 

■ Consider a block only if the person planning to do it is experi- 
enced and skillful; prepared to deal with its immediate effects and 
side effects (e.g., hypotension, respiratory depression, or paraly- 
sis); and able to provide followup assessment and treatment. 

■ Use radiographic control for blocks when ease and safety depend 
on the precise identification of landmarks. 

Catheter Placement for Drug Delivery 



Temporary spinal or epidural catheter placement is normally 
undertaken by specialists trained to recognize possible complications 
(e.g., opioid-induced respiratory depression or hypotension or sensori- 
motor blockade due to local anesthetic) and able to deal with these 
promptly and effectively. The need for dosage titration and coordina- 
tion of spinal with systemic medications and nonmedical therapies 
requires that the catheter be placed within the framework of multidis- 
ciplinary continuing care. Because identical materials and methods are 
often used for percutaneous epidural catheter placement for cancer 
pain and for acute postoperative pain control, anesthesiologists typi- 
cally perform these techniques and their specific followup. Factors to 
consider are presented in Table 12. The placement of catheters other 
than spinal ones, such as for drug infusion into interpleural or 
paravertebral areas, is uncommon, and few data other than case 
reports are available. 

98 



Invasive Therapies 

Percutaneous electrical stimulation for the relief of otherwise 
refractory cancer pain has likewise not yet been evaluated in 
controlled trials. Case reports — limited essentially to the percutaneous 
insertion of spinal cord electrodes for dorsal column stimulation — 
tend to focus on details of the method, to use nonuniform patient 
selection criteria, and to use heterogeneous pain assessment methods 
and followup duration. Not all experience is favorable (Meglio, Cioni, 
and Rossi, 1989). Hence, as Miles and colleagues wrote nearly 20 
years ago, "At this stage it seems sensible to concentrate effort on 
evaluating the method rather than on encouraging widespread and 
possibly indiscriminate use of what is an expensive use and relatively 
unproven technique" (Miles, Lipton, Hayward, et al., 1974). 

Neurosurgery 

Neurosurgical procedures for the relief of pain include neuroabla- 
tion, implantation of drug infusion systems, and neuroaugmentation. 
Published estimates of the percentage of patients who require neuro- 
surgical procedures to control cancer-related pain vary but are nearly 
all fewer than 10 percent. Nevertheless, long-standing clinical experi- 
ence supports a view that neurosurgical intervention is appropriate 
for patients in whom more conservative treatment is neither tolerated 
nor effective (or is unlikely to be effective) and for whom the exper- 
tise and followup care are available. The choice of procedure is based 
on the location and type of pain (somatic, visceral, deafferentation), 
the general condition of the patient, the life expectancy, and the 
expertise available. 

There is no simple, entirely safe procedure to alleviate cancer- 
related pain. Depending on the clinical setting and procedure, the 
risks of neurosurgical operation include new pain symptoms from 
nerve damage at the site of incision or nerve division, recurrence of 
pain after a transiently successful result, and postoperative neurologic 
impairment. These risks must be balanced against an ideal possible 
outcome of abolition of pain with little or no need for medication. In a 
particular clinical situation, a lack of personnel with experience in 
carrying out and following up other invasive therapies may warrant 
greater reliance on neurosurgical options (e.g., cordotomy instead of 
epidural catheter for pain of pelvic tumor). Because appropriate 
patient selection is essential, each proposed neurosurgical interven- 
tion is best reviewed by a team of oncologists, pain specialists, 
psychotherapists, and neurosurgeons. 

The following discussion addresses only procedures that are in 
general use and for which reported results can be meaningfully 
assessed. Classic (White and Sweet, 1969) and recent textbooks and 

99 



Management of Cancer Pain 

monographs provide current reviews of all of these procedures 
(Bonica, 1990; Gybels and Sweet, 1989; Patt, 1993). 

Neuroablation 



Peripheral Neurectomy. Currently, peripheral neurectomy for 
the control of cancer pain has largely been supplanted by other tech- 
niques, such as neuraxial opioid infusion or lytic nerve block. Multi- 
level neurectomy for chest wall pain is indicated when a discrete pain- 
producing lesion can be demonstrated to involve several intercostal 
nerves (Arbit, Galicich, Burt, et al., 1989). Neurectomy may also be 
effective in alleviating pain originating from a paraspinal tumor that 
involves a nerve or nerves at or distal to the neural foramen; it is often 
performed at the time of an operation on the spine (e.g., anterior or 
posterolateral vertebrectomy). Cranial neurectomies have selected 
indications in neuralgias resulting from cancer. The trigeminal and 
glossopharyngeal nerves can be ablated by radiofrequency lesions 
created by electrodes placed in either the foramen ovale (gasserian 
ganglion) or the jugular foramen or by chemical neurolysis at the 
gasserian ganglion (Giorgi and Broggi, 1984; Ischia, Luzzani, and 
Polati, 1990; Sweet, 1976). 

Dorsal Rhizotomy. Selective ablation of the dorsal nerve root 
reduces nociceptive perception in the affected area and spares motor 
function. Multilevel dorsal rhizotomy of all roots supplying an extrem- 
ity leads to a functionless limb. The likelihood of this impairment is 
lessened by sparing one dorsal root. In practice, this procedure is 
considered only for localized pain in the trunk or abdomen or, rarely, 
for an extremity that is functionless preoperatively (Arbit, Galicich, 
Burt, et al., 1989; Sindou, Fischer, Goutelle, et al., 1981). Dorsal 
rhizotomy can be accomplished by chemical neurolysis with radi- 
ographic guidance to place the tip of an infusion catheter at the 
precise segment within the epidural space. Surgical rhizotomy may be 
necessary if expertise in chemical neurolysis is unavailable or if it has 
been tried unsuccessfully. 

Anterolateral Cordotomy (Spinal Tractotomy). Anterolateral 
cordotomy is an ablative procedure aimed at the pain-conducting 
tracts in the anterolateral quadrant of the spinal cord. Cordotomy 
provides selective loss of pain and temperature perception several 
segments below and contralateral to the segment at which the lesion is 
placed. Anterolateral cordotomy is effective for unilateral, mainly 
somatic pain below the midcervical dermatomes (Ischia, Ischia, 
Luzzani, et al., 1985; Lahuerta, Lipton, and Wells, 1985). For visceral 
pain or bilateral pain, bilateral cordotomies may be required (Amano, 
Kawamura, Tanikawa, et al., 1991). Most cordotomies are currently 
done with the patient under local anesthesia by the percutaneous 

100 



Invasive Therapies 

route under fluoroscopic guidance, and the lesion is created by 
radiofrequency. The percutaneous approach avoids risks of open 
operation and anesthesia in patients in poor medical condition. 

Open cordotomies require a laminectomy and are most frequently 
performed at the low cervical or upper thoracic spine. Open cord- 
otomy may benefit patients in whom a percutaneous procedure has 
failed, those who cannot cooperate because of severe pain or confu- 
sion, those at risk for respiratory compromise, or those with bilateral 
pain in whom a bilateral, high cervical cordotomy carries additional 
risk of neurologic impairment. Potential complications include 
unmasking of dysesthetic pain; bladder, bowel, and sexual dysfunction; 
ataxia; paresis; and sleep apnea (Lahuerta, Lipton, and Wells, 1985; 
Tasker, 1988). 

Commissural Myelotomy. Commissural myelotomy disrupts 
pain-conducting fibers as well as a polysynaptic pain pathway that 
runs through the center of the spinal cord. Indications for myelotomy 
are bilateral and midline pelvic or perineal pain (Adams, Lippert, and 
Hosobuchi, 1988; van Roost and Gybels, 1989). The procedure may 
produce sphincter or motor dysfunction. Open myelotomy involves a 
multilevel laminectomy and exposure of the appropriate lumbar or 
sacral segments of the spinal cord. By use of an operating microscope, 
a midline incision is made and the spinal cord is divided vertically 
(Gildenberg, 1984). A cervicomedullary junction (extralemniscal) 
myelotomy that is performed stereotactically with CT guidance, local 
anesthesia, and intraoperative physiologic assessment can achieve 
pain relief over wide areas of the body including midline structures 
(Schvarcz, 1978). Potential complications include temporary dysesthe- 
sia and limb apraxia (Gildenberg, 1984). 

Hypophysectomy. Surgical and chemical (stereotactic transsphe- 
noidal) hypophysectomy are similar procedures that each offer a 40 to 
70 percent likelihood of pain relief (Levin, Katz, Benson, et al., 1980). 
The mechanism by which pain relief is achieved is unknown, but it is 
not related directly to the expected fall in the pituitary hormone levels, 
because pain relief is achieved in hormonally independent and depen- 
dent tumors (Katz and Levin, 1977; Lipton, Miles, Williams, et al., 
1978; Takeda, Fujii, Uki, et al., 1983). The clearest clinical indication is 
for bilateral or diffuse bone pain from metastatic disease that has failed 
to respond to all other hormonal, radiation, or medical therapies. 
Hormone replacement therapy is needed to replace pituitary secretion. 
Potential complications include endocrine deficits, damage to the optic 
nerves or oculomotor apparatus from the injected chemical agent, and 
CSF leakage (Cook, Campbell, and Puddy, 1984; Lahuerta, Lipton, 
Miles, et al., 1985; Lipton, Miles, Williams, et al., 1978). 

101 



Management of Cancer Pain 
Neuraxial Opioid Infusion 



In properly selected patients, intraspinal or intraventricular infu- 
sions of opioids have the advantage of producing profound analgesia 
without motor, sensory, or sympathetic blockade (Behar, Magora, Olsh- 
wang, et al., 1979; Bullingham, McQuay, and Moore, 1982). See Chapter 
3 and also the section on catheter placement in this chapter for a discus- 
sion of intraspinal and intraventricular routes of administration. 

Neuroaugmentation 



Interest in endogenous pain control systems as a therapeutic 
target began over 20 years ago in the context of the contemporaneous 
discoveries of the positive reinforcing quality of electric self-stimula- 
tion of the brain in animals and humans. Profound analgesia without 
drugs was reported in laboratory animals during electrical stimulation 
of the brain stem (Reynolds, 1969; Yaksh and Rudy, 1976). These 
effects appear to depend on the body's own opioids, endorphins. Since 
then, electrical stimulation for cancer pain control has been directed 
at deep brain structures such as the periaqueductal and periventricular 
grey areas (Meyerson, Boethius, and Carlsson, 1978; Young and 
Brechner, 1986), the limbic system (Gol, 1967), and other more super- 
ficial sites such as the pituitary gland (Yanagida, Suwa, Trouwborst, et 
al., 1988). Evaluation of the efficacy of electrical stimulation 
("neuroaugmentation") of deep brain structures for cancer pain relief, 
as for many other modalities, is difficult because of scanty descriptions 
of patients' diagnoses and limited pain assessment and followup, as 
well as the relatively few patients treated in this fashion compared 
with much larger numbers treated, e.g., with pharmacotherapy. 
Nonetheless, the few descriptive, uncontrolled published studies 
report partial or complete pain relief in 27 to 76 percent of patients 
treated by neuroaugmentation (Meglio and Cioni, 1982; Meyerson, 
1982; Young and Brechner, 1986). Published results of spinal cord 
stimulation for cancer pain relief are less encouraging. Meglio and 
others (Meglio, Cioni, and Rossi, 1989) reported, in a series of 109 
patients treated for pain relief by means of spinal cord stimulation, 
that none of the 11 who had cancer pain derived any clinical benefit, 
in contrast to favorable responses observed in patients with vasculo- 
pathic pain or postherpetic neuralgia. Similarly, others (North, 1993; 
Gybels, 1993; Marchand, 1993) have found spinal cord stimulation 
useful to treat chronic pain if not due to malignancy and only anec- 
dotal observations support the success of this modality in patients with 
cancer-related pain (Miles, Lipton, Hayward, et al., 1974; Nittner, 
1980; Raj, 1992). 

102 



Invasive Therapies 

Surgery 

Operations for the curative excision or palliative debulking of a 
tumor have the potential to reduce pain, improve prognosis, and even 
to achieve long-term, symptom-free survival. On the other hand, a 
tumor may be recognized to be unresectable at the time of operation. 
These perioperative dilemmas provoke anxiety in patients and their 
families, who worry not only about mortality but also about possible 
survival at the expense of function or loss of body parts. This anxiety 
may worsen pain. 

The surgeon's response to these issues can help to create a sense 
of personal comfort, to reduce the feelings of loss of control in 
patients confronted with a loss of autonomy, if not life itself, and to 
foster a clear understanding of the pain- and tumor-control goals of 
the surgical procedure and of how the procedure relates to other 
aspects of treatment. 

Postoperatively, the patient is often left with major changes in 
anatomy and physiology (e.g., laryngectomy, colostomy) that require 
further rehabilitation and continued attention to pain control. The 
surgeon should convey the nature and implications of the surgical 
intervention to the other members of the patient's management team 
and should continue in an advocacy role throughout the patient's 
course of care (Dunphy, 1976). 

Continuing surgical care is ideally provided in the context of an 
interdisciplinary approach with an attempt to avoid fragmentation and 
duplication. A vital part of surgical care for malignant disease is 
followup to contribute to improving quality of life, particularly the 
reduction of pain and suffering, to give assistance in rehabilitation, 
and to provide psychological support for the patient (O 'Young and 
McPeek, 1987). The patient and family seek assurance that the 
surgeon will not abandon them postoperatively and will be available 
for acute and chronic pain control. 

Surgical Management of Pain Due To Primary or 
Metastatic Tumor 

Pain control is usually a secondary goal when curative tumor exci- 
sion is performed. In contrast, when surgery is palliative because the 
tumor is unresectable, pain control is frequently the operative indica- 
tion. Cancer pain may arise through a variety of mechanisms that are 
amenable to relief by surgery. During curative or palliative procedures 
surgeons should use techniques to limit the development of chronic 
neuropathic pain such as nerve-sparing incisions, avoidance of 
ischemia, and careful dissection around nerves. The oncologic surgeon 

103 



Management of Cancer Pain 

should be familiar with the interactions of chemotherapy, radiation 
therapy, and surgical interventions so that iatrogenic complications 
may be avoided or anticipated (e.g., multiple fistulas resulting from 
bowel resection performed after radiation). 

Surgical procedures should proceed within a framework of basic 
surgical oncology principles that relate to both curative and palliative 
surgery. Among these is the fundamental principle that the first resec- 
tion offers the best opportunity for cure. Occasionally, an anatomic 
structure will need to be removed during this initial curative proce- 
dure to achieve a resection margin free of tumor. Careful preoperative 
and intraoperative weighing of the benefits of potentially curative 
procedures versus the risks of chronic pain and disability should be 
done with the patient preoperatively and confirmed by the surgeon 
intraoperatively. 

The second principle is that even outstanding radiotherapy gener- 
ally will not improve an inadequate surgical procedure. Depending on 
the natural history of a specific tumor system and anatomic 
constraints, postoperative radiotherapy can enhance local tumor 
control in patients with microscopically positive margins. However, 
radiotherapy may not provide long-term durable control of residual 
macroscopic gross malignant disease. Therefore, a surgical procedure 
undertaken for pain control is also most effective and durable if all 
gross disease can be resected. Short- and long-term pain control may 
be enhanced with postoperative radiotherapy. As a corollary to this 
principle, simple tumor debulking generally does not provide durable 
palliation for most patients. Growth of the residual tumor is sufficient 
to cause a rapid recurrence of painful symptoms. In such patients, 
radiotherapy alone may provide better palliation than an incomplete 
resection with its attendant pain. 

The third principle is that local tumor recurrence is not always the 
harbinger of disseminated disease. For example, local recurrence of 
soft tissue sarcoma or colorectal carcinoma does not always behave in 
this manner. Consequently, some patients with local recurrence can 
still be cured, depending on their underlying disease. Such patients 
may be best served by a second resection aimed at cure, perhaps 
incorporating radiotherapy, rather than a less aggressive palliative 
procedure solely for pain control. 

The fourth principle is that the timing of a surgical intervention for 
pain control is important. Understanding the natural history of a tumor 
system includes an awareness of the potential of a given tumor type for 
local invasion as well as tumor-specific patterns of metastasis. This 
addresses the issue of prospective palliation in which the effectiveness 
of surgical pain control may be maximized if undertaken before the 
onset of symptoms. For example, stabilizing a long bone with lytic 
metastases where fracture is likely or decompressing a spinal canal to 

104 



Invasive Therapies 

prevent impending paralysis or to relieve tumor nerve root entrapment 
may be most helpful as a timely intervention before the development 
of irreversible symptoms. This is in contrast to the asymptomatic 
patient with a recurrent, widely metastatic carcinoma of the colon that 
may eventually cause intestinal obstruction. In these instances, it may 
be better to monitor the patient closely for the development of symp- 
toms rather than intervene early and disrupt the quality of life. 

Pain as a Consequence of Operation 



Surgical procedures can cause several different forms of pain, 
including incisional pain. Depending on the resection and the specific 
tissues removed, patients may experience deep wound pain that may 
be more difficult to control. Finally, many patients may experience a 
variety of chronic pain syndromes after surgery (see Table 5). Some of 
these may not emerge until weeks or months after discharge. The 
surgeon should recognize and treat characteristic pain syndromes that 
follow specific surgical procedures (e.g., mastectomy, nephrectomy, etc). 

Careful surgical technique frequently can ameliorate the severity 
of postoperative pain. Gentle tissue handling; use of nerve- or vessel- 
sparing procedures; avoidance of tissue ischemia; careful neurolysis, 
performed as needed with a dissecting microscope; and selection of 
non-muscle-splitting incisions can contribute to less painful surgery 
and recovery. 

In the postoperative period, the surgeon should encourage the full 
use of the pain-control armamentarium. The management of patients 
with acute pain such as that caused by pathologic fracture, surgery, or 
diagnostic treatment procedures is described in detail elsewhere 
(Acute Pain Management Guideline Panel, 1992). 

The surgeon should assess the quality of postoperative pain 
control by frequent, direct patient contact. The surgeon without 
expertise in pain management should seek consultative help, particu- 
larly for the treatment of special populations. An integrated multidis- 
ciplinary pain control approach will maximize the usefulness of 
surgery as an adjunct of pain control in the patient with cancer. 



105 



6 



Procedure-Related Pain in 
Adults and Children 



Recommendations 

50. For patients of all ages, interventions for managing procedure- 
related pain and distress should take into account the type of 
procedure, the anticipated level of pain, and such individual 
factors as age and emotional and physical condition. (B) 

51. Sedation should be considered for painless procedures that require 
patient cooperation in remaining still, particularly for children 
under 6 years of age and for cognitively impaired patients. (B) 

52. Conscious sedation for procedural pain should be done in a 
manner that emphasizes safety and monitoring. (B) 

Patients with cancer undergo painful procedures for diagnosis, 
therapy, and supportive care, including lumbar puncture, bone marrow 
aspiration, and biopsy. Although venipunctures, insertion of intra- 
venous catheters, and intramuscular injections are less invasive, less 
painful procedures, their frequency and repetition become a major 
source of distress and apprehension. For aggressive treatment proto- 
cols, multiple invasive procedures may be performed weekly or daily. 

Children with cancer consider painful procedures to be the most 
difficult part of having cancer, and frequent repetition of procedures 
does not desensitize them to the distress (Fowler-Kerry, 1990; Weekes 
and Savedra, 1988). No published studies have focused on the reac- 
tions of adults to frequent and cumulative procedures, but some adults 
may be able to cope because of their greater cognitive ability and life 
experience in dealing with adversity and stress. Nevertheless, what is 
painful for a child or adolescent is also likely to be painful for an 
adult, especially when already stressed by the diagnosis of a poten- 
tially fatal illness. For all cancer patients, then, intervention for suffer- 
ing should include concern for and management of the pain and 
distress associated with procedures. 

Much of the data available on the management of procedure- 
related pain comes from studies on children with cancer and addresses 
nonpharmacologic management. For these guidelines, relevant data 
on cognitive-behavioral management in children were extrapolated to 
adults when there were no studies with adult patients. 

107 



Management of Cancer Pain 

Managing Procedure-Related Pain 

Painless procedures (such as CT scanning, MRI positioning for 
radiotherapy, and ultrasonic examination) that require patients to lie 
still, often on a cold, hard surface, may be frightening and indirectly 
provoke pain and distress. For patients older than 5 years, preparatory 
education about the sensations and surroundings the patient will expe- 
rience (Johnson, Rice, Fuller, et al., 1978) and the use of hypnosis, 
distraction, imagery (Katz, Kellerman, and Ellenberg, 1987; Zeltzer, 
Altman, Cohen, et al., 1990), and relaxation (Pfaff, Smith, and 
Gowan, 1989) may decrease distress and facilitate coping with the 
procedure. Sedatives, including oral chloral hydrate, pentobarbital, 
and midazolam (Sievers, Yee, Foley, et al., 1991), may be appropriate 
for painless procedures that require patient cooperation in remaining 
still, particularly for children under 6 years of age and for cognitively 
impaired patients. Because pharmacologic sedation may result in the 
loss of protective reflexes, patients must be closely monitored (Ameri- 
can Academy of Pediatrics Committee on Drugs, 1992). Intrinsically 
painful procedures may exacerbate ongoing cancer-related pain, and 
supplemental analgesia may be required (Table 20). 

Plans for managing pain associated with painful procedures should 
address several questions: 

■ Why is the procedure being performed? 

■ What is the expected intensity of pain? 

■ What is the expected duration of pain? 

■ What is the expected intensity of anxiety? 

■ What is the expected duration of anxiety? 

■ How often will the procedure be repeated? 

■ How do parents think their child will react? What reaction do 
adults predict for themselves? 

■ What is the meaning of the procedure for the patient and 
the family? 

Pharmacologic Strategies for Procedural Pain 

The needs of the individual and the type of procedure to be 
performed shape the pharmacologic approach to managing proce- 
dure-related pain. Because children have special needs, the practi- 
tioner's expertise and experience with children are key to successful 
therapy. For all patients, an opioid or a local anesthetic is needed to 

108 



Procedure-Related Pain 

Table 20. General principles of management for 
painful procedures 

General considerations 

Treat anticipated procedure-related pain prophylactically. 

Patients benefit from predictability as to time, frequency, and "clustering" of 
procedures, with an identified block of time when no procedures are to be 
performed, barring emergencies. 

Be attentive to the environment and to privacy. For children, a room other than 
the child's room should be used whenever possible. Environmental factors, 
such as cold or crowded rooms or "beepers" on machines, can escalate 
distress (Fowler- Kerry, 1990; Hester, 1989). 

Before beginning the procedure, manage preexisting pain as well as possible. 

Tailor treatment options to the patient's and the family's needs and prefer- 
ences, to the procedure, and to the context. 

Integrate pharmacologic and nonpharmacologic options in a complementary 
style. 

After the procedure, review with the patient and family their experiences and 
perceptions about the effectiveness of pain management strategies. 

Psychological preparation of the patient 

Provide adequate preparation of the patient and family. For children, discuss 
with the child and parents what can be expected and how the child might 
respond. 

Procedural considerations 

For procedures that will be repeated, maximize treatment for the pain and anxiety 
of the first procedure to minimize anxiety before subsequent procedures. 

Ensure the competency of the person performing the procedure and the 
timeliness of the procedure (Zeltzer, Altman, Cohen, et al., 1990). 

Minimize delays to prevent escalation of pain and anxiety (Fowler- Kerry, 1990). 

Provide monitoring and resuscitative equipment if drugs are used for sedation. 
Facilities, equipment, and trained personnel to manage emergencies (e.g., 
vomiting, inadequate ventilation, and anaphylaxis) should be immediately 
available (American Academy of Pediatrics Committee on Drugs, 1992; 
American Nurses Association, 1992). 

Nonpharmacologic interventions 

For children, allow parents to be with the child during the procedure, if parents 
choose to remain. The presence of a parent is a source of great comfort for the 
child (Bauchner, Waring, and Vinci, 1991). The parent's knowledge of the child 
can be valuable. Parents should be taught what to do, where to be, and what 
to say to help their child through the procedure. Parents should not be asked 
to restrain the child during the procedure. 

For adults, the presence of a supportive friend or relative may be helpful 
(Puntillo, 1990). Elicit the patient's preferences in this regard. 

Infants can benefit from sensory motor interventions (e.g., using a pacifier, 
touching, and patting) (Campos, 1989; NAACOG Committee on Practice, 
1991). Potentially effective cognitive-behavioral strategies for older children 

109 



Management of Cancer Pain 

Table 20. General principles of management for 
painful procedures, continued 

include distraction techniques such as music (Ryan, 1989), coping skills (Siegel 
and Peterson, 1981), hypnosis (Kuttner, 1988; Olness, 1981; Zeltzer and 
LeBaron, 1982), play therapy (Ellerton, Caty, and Ritchie, 1985), and thought 
stopping (Ross, 1984). Physical agents include TENS therapy (Eland, 1989) 
and counterirritants such as ice (Zeltzer, Altman, Cohen, et al., 1990). Cogni- 
tive-behavioral interventions that have been effective in reducing procedural 
pain or analgesic use in adults include imagery (Horan, Laying, and Pursell, 
1976) and hypnosis (Reeves, Redd, Storm, et al., 1983), and sensory and 
procedural information (Reading, 1982). Many of these methods, including the 
provision of preparatory information, hypnosis, thought stopping, and counter- 
irritation, may also be useful for adults. For all ages, choice should be based 
on the patient's preference, personality, and coping style. 

Pharmacologic interventions 

If possible, administer pharmacologic agents by a painless route (e.g., 
oral, transdermal, or intravenous). If parenteral agents are necessary and the 
patient does not have intravenous access, a single injection may be preferable 
to multiple attempts at insertion of an intravenous catheter. 



reduce the pain. Anxiolytics (i.e., medications for the relief of anxiety) 
and sedatives are used specifically to reduce anxiety before and during 
the procedure, but if used alone (i.e., without an analgesic), they may 
blunt the behavioral response without relieving the pain. Patients who 
have built up a tolerance to opioids or benzodiazepines may need 
much higher initial doses than those given in Table 21. 

Cardiovascular, hemodynamic, neurologic, or pulmonary instabil- 
ity are not absolute contraindications to systemic analgesia, but care- 
ful titration and monitoring should be provided. No agent should be 
used unless the clinician understands the proper technique of adminis- 
tration, the proper dosage, contraindications, side effects, and treat- 
ment of overdose. The use of systemic analgesics and sedatives should 
be approached differently in infants younger than 6 months of age 
(see Chapter 7). 

The mixture of meperidine, promethazine, and chloropromazine is 
not recommended even though commonly given intramuscularly for 
painful procedures in children. The efficacy of this mixture is contro- 
versial; disadvantages include the need for painful intramuscular injec- 
tion and the prolonged sedation associated with its use (Nahata, Clotz, 
and Krogg, 1985). 

Nitrous oxide, ketamine, thiopental, propofol, and methohexital 
can also be used as part of the pharmacologic strategy if trained 
personnel and appropriate monitoring procedures are available 
(Zeltzer, Jay, and Fisher, 1989). Administered by a mask or tent, 
nitrous oxide is a potent, short-acting inhalant analgesic that has been 

110 



Procedure-Related Pain 

Table 21. Pharmacologic agents for management of 
procedural pain 

Local anesthetics 

These agents may be administered by local infiltration or topical application. 
For topical use, an eutectic mixture of local anesthetics (EMLA) is efficacious 
in use with procedures and is now available in the United States (Kapelushnik, 
Koren, Solh, et al., 1990). When EMLA is used as a local anesthetic, it should 
be applied 60 to 90 minutes before the procedure. 

Opioids 

These drugs can be given via the intravenous or oral route. The intravenous 
route has the advantage of rapid effect and ease of titration. Intravenous 
opioids can be given in increments (e.g., 0.03 to 0.05 mg per kg of morphine 
every 5 minutes for children and other patients who weigh less than 50 kg, or 
2 to 4 mg of morphine every 5 minutes for adults and children who weigh more 
than 50 kg) and titrated to analgesic effect (Schechter, Weisman, Rosenblum, 
et al., 1990). Oral opioids can be used when close and rapid titration to effect 
is not required. 

Other opioids may be used instead of morphine. Meperidine is suitable for 
brief, titrated dosing but not for prolonged use. Intravenous fentanyl may be 
used in small doses (25-jxg increments, or 0.5 |xg/kg for patients who weigh 
50 kg or less). If given slowly in increments, the risk of chest wall rigidity is 
extremely small, but if it occurs, it should be managed immediately by the 
administration of a rapid-onset muscle relaxant and supporting ventilation. 
Transdermal fentanyl is not recommended for this indication because it 
requires on average 14 hours to reach peak application after administration 
(Varvel, Shafer, Hwang, et al., 1989). 

Benzodiazepines 

These agents can be given orally, intravenously, or transmucosally and provide 
anxiolysis, skeletal muscle relaxation, and in higher doses, amnesia. After 
opioids, intravenous benzodiazepines are given in increments and titrated to 
sedative effect (Sievers, Yee, Foley, et al., 1991 ; Zeltzer, Altman, Cohen, et al., 
1990). Unlike diazepam, midazolam does not cause pain and local sclerosis 
when given intravenously (Zeltzer, Altman, Cohen, et al., 1990). For adults, 
midazolam is traditionally titrated in increments of about 0.5 mg. Benzodi- 
azepines provide sedation, not analgesia, and hence, they often are used with 
opioids for painful procedures. If the combination of opioid plus benzodiazepine 
is used, the risk of respiratory depression is increased significantly, and careful 
titration and monitoring are required, particularly in the elderly. 

Barbiturates 

These drugs provide excellent sedation. They have no analgesic effects and are 
used with analgesics for painful procedures. Some patients may have paradoxi- 
cal reactions, and for most patients, the sedation persists for many hours after 
the procedure is completed (Zeltzer, Jay, and Fisher, 1989). As with benzodi- 
azepines, close observation for respiratory depression is essential, particularly 
when the intravenous route is used or if an opioid is coadministered. 



Ill 



Management of Cancer Pain 

used for procedural pain and in the treatment of refractory pain in the 
terminally ill. A significant drawback is the high degree of room air 
contamination, making occupational exposure a serious concern. 
Thus, although nitrous oxide may be valuable, its use should be 
limited to situations in which appropriate environmental adaptations, 
trained personnel, and monitoring procedures are in place (Miser, 
Ayesh, Broda, et al., 1988). General anesthesia is appropriate in 
certain situations (Zeltzer, Altman, Cohen, et al., 1990) such as when a 
young child must undergo a painful procedure. 

Sedation for Procedural Pain 

Skilled supervision is necessary whenever systemic pharmacologic 
agents are used for conscious sedation (i.e., the patient maintains a 
response to verbal and physical stimuli). At any site where painful 
procedures may be performed, patient-size-appropriate resuscitative 
equipment and resuscitative drugs should be immediately available to 
treat promptly any untoward effects. When conscious sedation is used, 
at least one health care professional who is well trained in airway 
management and advanced life support should be available. Patients 
should not eat or drink before procedures that use conscious sedation. 

During such procedures, a health care professional not involved in 
performing the procedure or restraining the patient should monitor 
the patient. Monitoring includes frequent assessment of heart rate, 
respiratory rate and effort, blood pressure, and level of consciousness. 
Continuous pulse oximetry to measure arterial oxygen saturation is 
strongly encouraged because visual observation of cyanosis is not 
sensitive to level of oxygen saturation. Guidelines from the American 
Academy of Pediatrics (1992) emphasize the importance of vigilant 
monitoring during conscious sedation: 

The caveat that loss of consciousness should be unlikely is a partic- 
ularly important aspect of the definition of conscious sedation, and 
the drugs and techniques used should carry a margin of safety wide 
enough to render unintended loss of consciousness highly unlikely. 
Since the patient who receives conscious sedation may progress into 
a state of deep sedation and obtundation, the practitioner should be 
prepared to increase the level of vigilance corresponding to that 
necessary for deep sedation, (p. 1112) 

After the procedure, monitoring should continue until the patient is 
fully awake and has resumed the former level of function. Discharged 
patients should be accompanied by an adult for a time at least as long as 
two half-lives of the agents used (e.g., at least 6 hours for morphine). 
These patients should be advised not to drive an automobile or operate 

112 



Procedure-Related Pain 

dangerous machinery until it is likely that all medication effects are 
resolved (usually 24 to 48 hours). Documentation of the monitoring 
during the procedure, observation before discharge, and discharge 
instructions should be part of the patient's permanent record. 

In contrast to conscious sedation, deep sedation (i.e., when the 
patient is not responsive to verbal or physical stimuli) is equivalent to 
general anesthesia and should be performed only under controlled 
circumstances by a professional trained in its use and skilled in airway 
management and advanced life support. Reference to specific published 
guidelines is recommended (e.g., in particular, American Academy of 
Pediatrics, 1985, 1992; American Nurses Association, 1991). 

Despite careful titration of sedative doses, individual responses 
are variable, and patients may occasionally have respiratory compro- 
mise or loss of airway reflexes. Because respiratory depression is 
strongly related to the degree of sedation, stimulation of the patient, 
and administration of small doses of naloxone (e.g., 0.04-mg doses for 
patients weighing 40 kg or more, or 0.5 to 2 |xg/kg for patients weigh- 
ing less than 40 kg), may be adequate to reverse mild degrees of 
hypoventilation (Schechter, Weisman, Rosenblum, et al., 1990). 
Assisted ventilation by bag and mask or (ultimately) by endotracheal 
intubation and repetitive naloxone dosing may be required to reverse 
severe degrees of respiratory depression. If such depression does 
occur, the patient should be observed until well after the naloxone 
effect has worn off (usually after 1 hour). 

Additional Pain Management Strategies for 
Lumbar Puncture and Bone Marrow Aspiration 

For lumbar punctures, local anesthetics are used, although efficacy 
in infants is controversial. Young children and some older children and 
adults benefit from a benzodiazepine. Supplementation with opioids is 
helpful for some patients, especially when difficulty in performing the 
procedure is anticipated. Patients over 5 years of age, who can effec- 
tively use cognitive and behavioral coping skills, may prefer not to use 
sedatives or opioids (Zeltzer, Altman, Cohen, et al., 1990). 

Management for bone marrow aspirations and biopsies includes 
the use, along with local anesthesia, of either general anesthesia or 
conscious sedation with benzodiazepines and opioids. Adequate time 
is necessary for the local anesthetic agent to have full effect. 

In children, nonpharmacologic methods with demonstrated effi- 
cacy for lumbar punctures and bone marrow aspirations and biopsies 
include hypnosis (Zeltzer and LeBaron, 1982); thought stopping 
(Ross, 1984); and a multidimensional psychological intervention that 
includes a breathing exercise, reinforcement, imagery, behavioral 

113 



Management of Cancer Pain 

rehearsal, and filmed modeling (Jay, Elliott, Ozolins, et al., 1985). 
These strategies alone, however, often do not reduce pain sufficiently. 

In addressing procedure-related pain, clinicians should consider 
the nature of the procedure (invasive or noninvasive), the degree of 
pain expected, and the needs of the patient in the development of a 
plan that emphasizes prevention of pain before the procedure. 
Further, especially in children, followup should include an assessment 
of pain secondary to the inflammatory process and provision of treat- 
ment (e.g., applications of cold or heat unless contraindicated or use 
of mild analgesics or NSAID). 






114 



f Pain in Special Populations 

Recommendations 

53. Clinicians should give special attention to the assessment and 
treatment of pain in special populations, including the very young 
and very old, cognitively impaired, known or suspected substance 
abusers, and non-English-speaking persons. (Panel Consensus) 

54. Behavioral observation should be the primary assessment method 
for preverbal and nonverbal children and used as an adjunct to 
assessment for verbal children and cognitively impaired adults. 
(Panel Consensus) 

55. Infants, especially nonventilated, should be closely monitored 
when they are administered opioids because opioid clearance is 
prolonged and the blood-brain barrier is more permeable, which 
increases their potential for opioid-induced sedation and respira- 
tory depression. (A) 

56. The elderly are more vulnerable to drug accumulation because of 
age-related changes in pharmacokinetics of analgesics; aggressive 
pain assessment and management are as necessary for them as for 
younger age groups. (A) 

57. When new psychiatric symptoms occur in a patient with cancer, 
the possibility of uncontrolled pain should be considered. (Panel 
Consensus) 

58. Uncontrolled pain, an important factor contributing to feelings 
of hopelessness, suicidal ideation, and requests for physician- 
assisted suicide or euthanasia, should be aggressively assessed 
and treated. (B) 

59. Because patients with current substance abuse disorders are at 
risk for undertreatment of cancer pain, their care should be 
managed by clinicians knowledgeable in both pain management 
and substance abuse. (Panel Consensus) 

60. Nonopioid analgesic modalities should not be substituted for 
opioid analgesics to treat severe pain in the suspected or known 
substance abuser. (Panel Consensus) 

61. When assessing pain or developing a pain treatment plan, health 
care clinicians should be aware of the unique needs and circum- 
stances of patients from various ethnic and cultural backgrounds. 
(Panel Consensus) 

115 



Management of Cancer Pain 

62. Because patients with HIV positive/ AIDS often have pain prob- 
lems similar to those of patients with cancer, recommendations for 
pain assessment and management in this guideline are generally 
applicable for pain in these patients. (B) 



Pain in Neonates, Children, and Adolescents 

Most children with cancer experience pain (McGrath, 1990b), 
which, as does the progression of cancer in children, differs from that 
of adults. After diagnosis, the common childhood malignancies gener- 
ally respond rapidly to treatment, and disease-related pain often 
remits. If the tumor recurs and is resistant to treatment, the disease 
progresses rapidly, resulting in early death (Miser, 1993). 

Pain in children with cancer arises more often from the treatment 
than from the disease (Miser, Dothage, Wesley, et al., 1987). Aggres- 
sive multimodal treatment protocols for children have increased 
survival rates markedly for most types of cancer, but they often 
involve treatment toxicity that results in painful conditions, e.g., 
mucositis, peripheral neuropathy, and infection. 

Children with cancer undergo procedures ranging from venipunc- 
tures to bone marrow aspirations and biopsies. Children with aggressive 
treatment protocols may have one or more venipunctures daily, lumbar 
punctures weekly, and bone marrow aspirations monthly. Unlike adults, 
infants and children do not provide consent for these procedures and 
often do not understand the reasons for them or realize their short 
duration. Although appropriate preparation and adequate analgesia are 
crucial for children undergoing procedures, often neither occurs or they 
occur in a haphazard fashion (Schechter, 1989). 

The optimal treatment of a child's cancer-related pain requires an 
awareness of the many factors that shape that pain. Among these are 
the child's developmental level, emotional and cognitive state, person- 
ality traits, physical condition, and past experiences; the meaning of 
the pain for the child; the stage of the disease; the child's fears and 
concerns about illness and death; issues, attitudes, and reactions of the 
family; cultural background; and the environment (Hester, Foster, and 
Beyer, 1992). Clinicians should be aware that children with cancer 
experience many distressing symptoms such as pain, depression, anxi- 
ety, panic, pruritus, fatigue, nausea, constipation, insomnia, dyspnea, 
and the fear of abandonment and death. 

Getting to know the child and having knowledge of developmen- 
tal norms and behavioral competencies are important in the assess- 
ment and management of pain. Clinicians should tailor assessment 
and management strategies to the child's developmental level, 

116 



Pain in Special Populations 

personality style, and emotional and physical resources and to the 
context; tailoring is particularly necessary for children with develop- 
mental delays, learning disabilities, emotional disturbances, and 
language barriers. 

Assessment is not only diagnostic but also therapeutic. Assessing 
the meaning of the pain to the child and the family, the effect of the 
pain on the activities of daily living and on mood, and the concurrent 
concerns and symptoms helps clinicians understand pain from the 
perspective of the child and the family. Asking about pain underscores 
the clinician's desire to ease pain and suffering and builds a therapeu- 
tic alliance with the child and family. 

It is easier for clinicians to understand inherently subjective expe- 
riences, such as pain, anxiety, and despair, when the child can verbal- 
ize, but for some children, verbal communication is difficult or impos- 
sible. Therefore, the clinician should recognize the potential for pain 
and discomfort or suspect that the child is in pain even if the signs are 
not immediately apparent. 



Assessment 



Whether the child is at home, in a clinic or clinician's office, or at 
the hospital, assessment of pain should occur during the course of his 
or her illness. Critical to assessment is open communication about 
pain among the child, the family, and the health care team. 

An initial pain history focuses on understanding pain from the 
child's and family's perspective. Central to communicating with the 
child about pain is determining the language the child uses for pain 
(e.g., hurt, owie, boo-boo) and how and to whom the child communi- 
cates pain. Other issues include past pain experiences, the child's 
response to pain, expectations related to pain, and preferences for 
assessing and treating pain (see Attachment B). Clinicians should 
integrate this background information into subsequent assessments 
and treatment plans for the child. 

A routine assessment of pain is critical to ongoing management. 
The frequency of assessment should be tailored to the severity of the 
pain, the context, and the preferences of the child and family. 
Frequent assessments are necessary when pain is being poorly 
managed or is not responding to the current treatment. Documenta- 
tion of pain ratings on a chart or flowsheet, located in a visible place 
such as at the bedside, provides easy access for providers. The use of a 
flowsheet reduces the possibility of redundant questioning which can 
be overwhelming for the child and family and may interfere with the 
child's coping skills. 

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Management of Cancer Pain 
Methods for Assessing Pain. 



Assessment of children's pain involves one or more of the follow- 
ing approaches: self-reports, proxy reports, observations, and physio- 
logic measures. "Because physiologic indicators such as heart rate, 
respiratory rate, blood pressure, and diaphoresis alter with a variety of 
stress-arousal events, they should not be used as measures of pain in 
the absence of other pain assessment methods or clinical indicators" 
(McGrath, de Veber, and Hearn, 1985). A variety of assessment meth- 
ods are available, but no one approach provides a complete picture of 
the pain experience. At least one method that is reliable, valid, and 
developmentally appropriate to the child should be used regularly for 
assessing pain. Because children with cancer may need assessment in 
settings other than hospitals (e.g., their homes), the methods should 
be affordable and easy for parents or other caregivers to use. 

Self-Report. Self-report methods provide the most reliable and 
valid estimates of pain intensity and location. These methods are 
appropriate for children over the age of 4 who can verbalize 
(McGrath, 1990b). Rarely will children with cancer fabricate pain 
(Ross and Ross, 1988), but they may deny or underreport pain if they 
(1) fear that admission of pain will mean further painful procedures or 
treatments such as "a shot for pain"; (2) lack awareness that pain can 
be treated; (3) wish to protect parents from the reality of progressive 
disease; or (4) desire to please and placate others. 

Self-report methods should be easy to administer with simple 
instructions for children. They should allow both verbal and nonver- 
bal (e.g., pointing) responses. Often, children will not respond to ques- 
tions verbally, especially if they are anxious or depressed or are expe- 
riencing severe pain. 

Several self-report methods for pain intensity are available for use 
with children (see Attachment B). Although the psychometric 
adequacy of these methods for children with cancer has yet to be deter- 
mined, reliability and validity estimates are available for other pain 
syndromes such as postoperative pain, procedural pain, and juvenile 
rheumatoid arthritis. Methods appropriate for children over the age of 
4 years include the Oucher (Beyer, Villarruel, and Denyes, 1993) and 
the Poker Chip Tool (Hester, Foster, and Kristensen, et al., 1989). 
Some investigators have used cartoon faces as scales of measurement 
for young children with cancer who are undergoing procedures, but the 
construct being measured was not necessarily pain. One scale measures 
pain affect (McGrath, de Veber, and Hearn, 1985), whereas others 
measure intensity of pain, anxiety, or distress (Adams, 1990; LeBaron 
and Zeltzer, 1984). Children over the age of 7 years who understand 
the concepts of order and number may prefer a numerical rating scale 
(NRS) (McGrath and Unruh, 1987), a horizontal word graphic rating 

118 



Pain in Special Populations 

scale (Savedra, Tesler, Holzemer, et al., 1989 [updated 1992]), or a VAS 
(McGrath, 1990b). A large study that included children and adoles- 
cents reported that the VAS was the least preferred of five horizontal 
pain scales (Tesler, Savedra, Holzemer, et al., 1991). 

To determine the location of pain, children can be asked either to 
point to their body or use a body map (i.e., an outline). Children over 
the age of 4 can use crayons or colored markers to locate pain on a 
body map (Eland, 1989; Savedra, Tesler, Holzemer, et al., 1989 
[updated 1992]) (see Attachment B). The precision of the location will 
increase with the child's age. Children who are suffering may regress; 
similarly, children who are developmentally delayed or learning 
disabled may need assessment tools developed for younger children. 
If a child is unable or unwilling to provide pain ratings, parents or 
health care professionals can provide proxy reports. Proxy ratings, 
however, are inexact. 

Behavioral Observation. Behavioral observation is the primary 
assessment approach for preverbal and nonverbal children and is an 
adjunct to assessment for verbal children. Observations focus on 
vocalizations (e.g., crying, whining, or groaning), verbalizations, facial 
expressions, muscle tension and rigidity, ability to be consoled, guard- 
ing of body parts, temperament, activity, and general appearance. 
Adequate reliability and validity documentation is lacking for behav- 
ioral observations; consequently, most such observations offer only a 
second-best approximation of the child's experience, even though clin- 
icians often attribute greater importance to nonverbal expression than 
to self-report (Craig, 1992). Changes in how a child looks and acts 
may indicate the onset of pain or its increase (Hester and Foster, 
1990) and warrant further investigation and documentation. 

Observations are problematic in that the stimulus for behaviors or 
changes is not always clear. For example, children cry in response to 
pain, as well as fear, loneliness, and overstimulation. Clinicians may 
misinterpret behaviors such as sleeping, watching television, and using 
humor as the absence of pain when, in fact, the child is attempting to 
control pain. Moreover, behavioral responses may be absent or atten- 
uated when vocalizations or movements cause or increase pain. 
Infants may become apathetic after only a few days of continuing 
severe pain, and suffering experienced by older children and adoles- 
cents with cancer may blunt behaviors and affect. Other factors that 
inhibit behavioral responses include intubation, use of paralyzing 
agents or sedatives, extreme illness, weakness, or depression. There- 
fore, the use of behavioral observation to guide analgesia requires 
close attention to the context. If caretakers are not sure whether a 
behavior indicates pain and if there is reason to suspect the presence 
of pain, a trial of analgesics can be diagnostic as well as therapeutic. 

119 



Management of Cancer Pain 

Most of the scales developed for measuring behaviors address 
postoperative pain or pain associated with invasive procedures (e.g., 
LeBaron and Zeltzer, 1984). Given the nature of cancer-related pain, 
behavioral scales for the assessment of acute pain problems are 
unlikely to be sensitive in assessing the child with cancer pain. The 
Gustave-Roussy Child Pain Scale (Gauvain-Piquard, Rodary, 
Rezvani, et al., 1987) is the only observation tool developed for chil- 
dren with cancer pain. 

Pain Management 



Pain is managed within a therapeutic alliance among the child, 
his or her parent(s), nurses, physicians, and other health care pro- 
fessionals. The beliefs and preferences of the child and family should 
be elicited, respected, and carefully considered. At the same time, 
the primary obligation of the health care professional is to ensure 
safe and competent care. The presence of divergent beliefs and goals 
among members of the team can interfere with effective pain and 
symptom management, but these can often be resolved through 
discussion and negotiation. 

Medical Interventions. Medical interventions include analgesics, 
adjuvant agents (e.g., corticosteroids, tricyclic antidepressants, stimu- 
lants), palliative chemotherapy, radiation therapy, regional analgesia, 
and neurosurgical approaches. In most cases, analgesics — either alone 
or supplemented with chemotherapeutic agents, radiation therapy, 
and adjuvants — provide adequate pain relief. Regional analgesia is 
occasionally helpful. 

Analgesics and Adjuvants. Health care professionals treating 
children often use medications that have not been specifically tested 
in children and that are thus not specifically indicated for pediatric 
use. This situation exists because children as a group are therapeutic 
"orphans"; the small number of children needing certain medications 
does not provide incentive for widescale testing. The administration of 
analgesics to children should follow the WHO's ladder approach (see 
Chapter 3). Usual doses for children are listed in Tables 8 and 10. 

Acetaminophen and NSAIDs. Acetamenophen is a useful and 
relatively safe analgesic that provides effective relief of mild pain and 
enhances opioid effectiveness (Tobias, 1992). The rectal route is avail- 
able for children who cannot take medication orally; however, chil- 
dren do not like this route and may refuse to take the medication. 
Rectal administration is contraindicated for children who are 
neutropenic or thrombocytopenic and for those with mucositis. These 
contraindications and the irregular absorption of the rectal route limit 
its usefulness in treating severe pain (Miser and Miser, 1989). 

120 



Pain in Special Populations 

Because children with cancer are often thrombocytopenic, 
NSAIDs frequently cannot be used. They do, however, provide excel- 
lent analgesia for the child who is not at risk for bleeding because of 
thrombocytopenia or a coagulopathy and who is not at unusual risk of 
gastritis or ulceration (e.g., from the concurrent use of corticosteroids). 
NSAIDs effects on inflammation can be salutary, especially in the 
presence of bone pain. Evidence suggests that NSAIDs such as 
choline magnesium trisalicylate and salsalate have little effect on 
platelet function in normal subjects not at risk for bleeding (Cronin, 
Edmiston, and Griffin, 1991). Even so, the use of these "platelet-spar- 
ing" NSAIDs in children at risk for bleeding is not recommended. 

The administration of acetaminophen and NSAIDs varies accord- 
ing to the severity of the pain (Table 9). For very mild or intermittent 
pain, as-needed administration is appropriate. However, hospitalized 
children and their parents should be told to ask for the medication if 
pain occurs. An advocate may be appointed to assist the child and 
parents in requesting medications. For continuous or more severe 
pain, around-the-clock administration is necessary (Table 9). 

Opioid analgesics. For moderate to severe pain, opioid analgesics 
are recommended. Some health care professionals are concerned 
about the potential for addiction in children, a risk that is rare in adult 
cancer patients (Kanner and Foley, 1981). Although studies of the 
risks in children are lacking, no known aspect of childhood develop- 
ment or physiology increases the risk of physiologic or psychological 
vulnerability to chemical dependence. Therefore, withholding opioids 
from children with cancer is unwarranted. 

Route of administration. Whenever possible, opioids should be 
administered orally. Many are available in a liquid form or suspension; 
often, those that are not commercially available in this form can be 
pulverized (with the exception of controlled-release drugs) and 
administered in a small amount of liquid or soft food. 

Parenteral administration is indicated when: 

■ The child cannot take medication by mouth, for reasons such as 
obstruction, nausea, vomiting, and mucositis. 

■ Absorption may be compromised (e.g., as a result of chemotherapy- 
induced obstipation). 

■ The pain is severe and requires timely management and a rapid 
titration to effect. 

■ Frequent and severe breakthrough or incident-related pain occurs. 

■ The oral route requires frequent administration of medication or 
large numbers of pills or liquid. 

121 



Management of Cancer Pain 

Even with severe pain, once the opioid dose requirement is ascer- 
tained, the route can be changed over a few days from the intravenous 
to the oral route by using equianalgesic conversions (Table 11). 

When parenteral administration is required, the intravenous or 
subcutaneous route can be used (Miser, Moore, Greene, et al., 1986). 
Some children with cancer have implanted central catheters, which 
can be used; similarly, children who cannot take medication by mouth 
often have an intravenous catheter for the administration of fluids, 
chemotherapy, or antibiotics. Intramuscular injections should not be 
used, because "shots" are painful and frightening to children. 

Transdermal fentanyl provides an alternative route for children 
with relatively constant pain who require larger doses of opioid analge- 
sia. It is unsuitable for rapid-dose titration or for any patient with 
changing pain intensity. Currently available preparations do not permit 
the delivery of drug at dosage rates low enough for young children. 

Schedule and dose. Severe pain is an emergency, requiring the 
rapid titration of analgesia to provide relief within a few hours. Rapid 
titration involves frequent assessments and dosage adjustments. For 
example, because the peak effect of intravenously administered 
morphine occurs about 15 minutes after administration, the patient 
whose dose requirement is unknown could be given 0.1 mg/kg of 
morphine and be assessed every 15 minutes, with additional incre- 
ments of 0.05 mg/kg administered until relief is obtained. 

Opioids can be administered by intermittent bolus injections, infu- 
sions, or infusions with "rescues." Unless the pain is truly intermittent 
and unpredictable, as-needed administration should not be used since 
delay between the request for medication and the administration 
results in poor pain management. In those isolated cases when as- 
needed administration is indicated and when "rescue" doses of 
medication are added to an infusion, the child needs an advocate 
(e.g., nurse, parent) to ensure prompt administration. 

Intermittent bolus injections of morphine or its analgesic equiva- 
lent can be provided on an around-the-clock basis at a starting dose of 
about 0.1 mg/kg. Initial dose intervals are the same as those recom- 
mended for adults. Continuous infusion of morphine, at a starting 
dose of 0.02 to 0.04 mg/kg per hour for children over 6 months of age 
has been well studied in postoperative pain and described in cancer- 
related pain (Hendrickson, Myre, Johnson, et al., 1990; Miser, Moore, 
Greene, et al., 1986). 

Continuous infusion avoids the extreme variations that may 
occur with intermittent intravenous doses and is indicated when 
intermittent doses: 

■ Cause undue somnolence at the time of peak effect. 

■ Provide inadequate analgesia at the usual starting doses. 

122 



Pain in Special Populations 

■ Must be administered more frequently than every 2 to 3 hours to 
provide adequate analgesia. 

Children receiving a continuous infusion should be offered "rescue" 
doses for breakthrough or poorly controlled pain regularly on the 
basis of their level of pain and the duration of the effect of the 
prescribed opioid. 

Because of wide variability in opioid dose requirements (Nahata, 
Miser, Miser, et al., 1984), pain and side effects should be assessed 
frequently, with the dose and interval adjusted for optimal relief. 
Many children require large doses of opioids; the process for dose 
increase and titration to effect is the same as in adults (see Chapter 3). 
To titrate to effect when a continuous infusion with rescue doses is 
used, the total amount of opioid administered (including rescue doses) 
is calculated for a specific time period, usually 8 or 12 hours. This 
amount is then added to the total amount of opioid to be infused over 
the next 8- or 12-hour period. Because four or five half-lives are 
required to reach a new steady state, increasing the infusion when 
pain is poorly managed will not by itself provide adequate, immediate 
relief. In fact, it could result in the administration of an unnecessarily 
large dose as soon as the infusion reaches a new steady state. 

Agent. Morphine is the preferred starting agent for severe pain. 
Codeine and oxycodone can be used for moderate pain, although 
morphine and hydromorphone may be better tolerated by some chil- 
dren. Opioids such as hydromorphone, methadone (Miser and Miser, 
1986), and fentanyl may be preferable when side effects are not easily 
controlled. Methadone use requires careful titration and appreciation 
of the potential for delayed somnolence because of its long half -life. 
Meperidine should be used only in exceptional circumstances such as 
hypersensitivity to morphine and hydromorphone and when a single 
dose (e.g., for a procedure) or use for fewer than 2 days is anticipated. 

Patient-controlled analgesia (PC A). PC A provides safe and 
effective analgesia in children old enough to understand the relation- 
ship among a stimulus (pain), a behavior (pushing the button), and a 
delayed response (pain relief). Most children over the age of 7 under- 
stand this concept, and sometimes even younger children can learn to 
use PCA, but some may not have the cognitive or emotional resources 
to use it. Only one postoperative pain study has focused on the effec- 
tiveness of PCA with and without a basal infusion in contrast to the 
effectiveness of intramuscular morphine (Berde, Lehn, Yee, et al., 
1991). One study addressed the efficacy of PCA for adolescents (age 
18 or older) with cancer in treating mucositis after bone marrow trans- 
plantation (Hill, Chapman, Kornell, et al., 1990). Patient-controlled 
dose and basal infusion have not been explored systematically in 
children with cancer. 

123 



Management of Cancer Pain 

Monitoring. Regular assessment of a patient's vital signs and level 
of consciousness is necessary when parenteral opioids are used. 
Because of variable clinical situations and goals of treatment in chil- 
dren with cancer-related pain, professional judgment should be used 
to determine the presence, type, and frequency of monitoring. 
Because of wide interindividual and intraindividual variations in 
response, a child may have an adverse reaction, despite the most care- 
ful titration of doses and intervals. 

Side effects. Young children may have difficulty communicating 
subjective symptoms like pruritus, nausea, constipation, and dyspho- 
ria; the preverbal child may show only generalized discomfort. If an 
infant or preverbal child becomes increasingly restless or irritable, 
despite an increased opioid dose, it is important to consider treatment 
of presumed side effects or a change to an alternative opioid. The 
pharmacologic approach to managing side effects in children is similar 
to that in adults. However, the assessment of side effects and pain 
relief should occur simultaneously. 

One of the most feared side effects of opioid use is respiratory 
depression. In the dying patient, it may be due to the disease and not 
necessarily to the effects of opioids. In the patient who is not dying, 
naloxone may be indicated. If naloxone is used, it should be titrated 
incrementally (see Chapter 3) until the patient resumes adequate 
respiratory effort. The initial dose of naloxone in the child is about 0.5 
to 2 |ULg/kg, with the dose repeated about every minute. Physical stimu- 
lation, oxygen administration, and support of respiration can be used 
while titrating the naloxone to effect. 

Adjuvants. Tricyclic antidepressants can be used as described for 
adults in Chapter 3. In general, the starting dose should be low, (e.g., 
about 0.2 mg/kg of amitriptyline), and then increased to about 1 to 2 
mg/kg daily. Tricyclic antidepressants should be used with care in chil- 
dren who have received large doses of cardiotoxic anthracyclines. A 
baseline electrocardiogram may be useful but is not required. 

Stimulants such as dextroamphetamine and methylphenidate can 
also be used for children, with the goal being to provide additional 
analgesia and increased quality of awake time. The starting dose for 
both stimulants, 0.05 mg/kg, is gradually increased to effect with an 
upper limit of roughly 0.25 mg/kg per dose. Stimulants are given at 
times of desired wakefulness, such as morning and midday. 

Analgesics for Neonates and Young Infants. Acetaminophen can 
be safely administered to neonates and infants without concern for 
hepatotoxicity when given for short courses at the recommended doses 
(Berde, 1991). Acetaminophen can be given to augment analgesia. 

The use of opioids in young infants requires special consideration 
and expertise. Young infants, especially premature babies or those who 
have neurologic abnormalities or pulmonary disease, are susceptible to 

124 



Pain in Special Populations 

apnea and respiratory depression when systemic opioids are used 
(Purcell- Jones, Dormon, and Sumner, 1987). The infant's metabolism is 
altered so that the elimination half-life is longer and the blood-brain 
barrier is more permeable (Collins, Koren, Crean, et al., 1985; Lynn 
and Slattery, 1987). Both factors result in young infants having higher 
in-brain concentrations of opioids for a given dose than do mature 
infants or adults. Intensive monitoring is reasonable up to about 1 year 
of age for nonventilated infants who are receiving opioids because 
extreme sedation and decreased respiratory effort may be difficult to 
assess. Institutions where neonates and infants are treated for cancer 
should train personnel in the effective and safe administration of anal- 
gesia and provide appropriate technologies for monitoring. 

Some evidence suggests that the clearance of opioids increases 
rapidly over the first few weeks of life and approaches adult levels by 
the time the infant is 1 to 2 months old (Hertzka, Gauntlett, Fisher, et 
al., 1989; Koren, Butt, Chinyanga, et al., 1985). Because available data 
are based on small numbers of infants, many practitioners reduce the 
initial dose and use intensive monitoring for infants up to 6 months of 
age; this age is arbitrary and represents a cautious interpretation of 
the literature. 

Although further research is necessary, apnea and respiratory 
depression appear to be dose related (Koren, Butt, Chinyanga, et al., 
1985). For nonventilated infants under 6 months of age, the initial 
opioid dose, calculated in milligrams per kilogram, should be about 
one-fourth to one-third of the dose recommended for older infants 
and children. For example, 0.03 mg/kg of morphine could be used 
instead of the traditional 0.1 mg/kg. Careful assessment is necessary so 
that the optimal dose and interval of administration can be deter- 
mined from clinical parameters (e.g., when pain occurs and whether 
the infant appeared comfortable). Many infants have inadequate pain 
relief after the initial small dose and require upward titration, some- 
times to doses equivalent to those used for older children. Continuous 
infusions can be used as long as the infusion begins with a conserva- 
tive starting dose, which is then titrated upward until pain is relieved. 

Aggressive monitoring, when necessary, should include frequent 
assessments and close observation of heart and respiratory rates, 
respiratory effort, blood pressure, and level of alertness as determined 
by responsiveness to stimuli. Frequent or continuous assessment of 
arterial oxygen saturation with pulse oximetry is a valuable adjunct to 
clinical observation. Because of delayed absorption, opioid levels in 
serum may increase many hours after a one-time intramuscular or 
subcutaneous dose in infants who are opioid naive; monitoring, there- 
fore, should be continued for 12 hours after an opioid dose (Koehn- 
top, Rodman, Brundage, et al., 1986). 

125 



Management of Cancer Pain 

Epidural Analgesia. The use of epidural analgesia is appropriate 
when systemically administered oral or parenteral analgesics do not 
achieve adequate pain relief without unacceptable sedation, respiratory 
depression, or other side effects. Epidural analgesia is now widely used 
for infants and children with postoperative pain. The hemodynamic and 
respiratory effects of major regional analgesia in infants with postopera- 
tive pain appear minimal (Meignier, Souron, and Le Neel, 1983). 
Systematic studies on epidural analgesia for children with cancer are 
unavailable, but experience in a few pediatric centers suggests that 
some children can be made comfortable with epidural or subarachnoid 
infusions of opioids and local anesthetics. For pediatric epidural infu- 
sion rates, the maximal recommended local anesthetic rates, per hour, 
are roughly 0.4 mg/kg for bupivacaine and 2 mg/kg for lidocaine. 
Epidural infusions that exceed those recommended rates may lead to 
convulsions (Berde, 1992). Epidural morphine has been used success- 
fully even for young infants with cancer (Berde, Fischel, Filardi, et al., 
1989). The proper use of infusions or intermittent doses of peridural 
opioids or local anesthetics requires expertise and close monitoring. 



Nonpharmacologic Methods. 



Although little research has focused on the use of cognitive-behav- 
ioral methods for children with cancer, they have a potentially impor- 
tant role in relieving pain, and the methods used by adults can be 
adapted for children. For example, distraction techniques might 
involve reading or telling a favorite story, talking about the story's 
characters, or playing video games. Preparation for painful events 
could involve the use of a puppet, a favorite cartoon character, or an 
animal. Stuffed animals with inserted audiotapes of stories or music 
may help to induce a state of relaxation. Something familiar to the 
child may facilitate participation in these nonpharmacologic strategies. 

When a child is in pain, the presence of a parent is usually helpful. 
Other methods of psychological support include holding someone's 
hand, a stuffed toy, or favorite blanket; asking questions; using distrac- 
tion; sleeping and resting; relaxing or using imagery; changing posi- 
tions; and engaging in humor; these seemingly simple interventions 
can have powerful effects. Facilitating the child's usual strategies for 
decreasing pain is important. Although not well researched in child 
populations, measures such as physical therapy, TENS (Eland, 1989), 
splinting a painful extremity, positioning, the application of heat or 
ice, and massage may help relieve pain (see Chapter 4). 

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Pain in Special Populations 



Assessing the Adequacy of 
Pain Management Strategies. 



The most important consideration in the management of pain in 
children with cancer is the provision of a child-centered environment 
and attitude. Health care professionals should understand and consider 
developmental issues and problems that affect the integrity and struc- 
ture of the family. Child-centered cancer care provides the necessary 
items and services to support the child and the family emotionally, 
socially, and spiritually throughout the treatment process. In such an 
environment, pain and suffering are continually assessed, and appro- 
priate supportive measures are introduced. Otherwise, the treatment of 
pain with analgesics and other agents will often be inadequate. 

Optimal assessment and treatment require a knowledge of chil- 
dren's development, behavior, and physiology. Because children are less 
likely than adults to talk about pain, the responsibility to inquire about 
pain rests with the health care professional (Table 22). Some children 
will have pain that is particularly difficult to manage. In these situations, 
consultation with specialists in children's pain is recommended. 



Elderly Patients 

Elderly patients are often undertreated for cancer pain. Attitudes 
of health care professionals, the public, and patients toward pain can 
impede appropriate care; because many people consider acute and 
chronic pain to be a part of normal aging. In some instances, pain is 
not assessed because elderly patients, who may be confused, have 
difficulty communicating their pain to health professionals. In other 
instances, clinicians have mistaken beliefs about decreased pain sensi- 
tivity and heightened pain tolerance in the elderly. Frequently, the 
elderly are given nonopioids or weak doses of medications because 
their care providers mistakenly believe that they cannot tolerate 
opioid agents. 

The elderly should be considered an at-risk group for the under- 
treatment of cancer pain because of inappropriate beliefs about 
their pain sensitivity, pain tolerance, and ability to use opioids. 
Elderly patients, like other adults, require aggressive pain assessment 
and management. 

Pain management in the elderly presents several challenges, 
including the discrepancy between the high prevalence of pain in the 
elderly and the limited attention to this group in the research litera- 
ture and in medical and nursing texts (Ferrell, 1991). Of all reports 
about pain published annually, fewer than 1 percent focus on pain 
experience or syndromes in the elderly (Melding, 1991). Current 

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Management of Cancer Pain 

Table 22. Checklist for assessing adequacy of 
pain management in children 

Pharmacologic strategies 

Have the child and parent(s) been asked about their previous experiences with 
pain and their preferences for use of analgesics? 

Does the child or parent(s) have reservations about the use of opioids for pain 
treatment? 

Is the child being adequately assessed at appropriate intervals? 

Are analgesics ordered for prevention and relief of pain? 

Is the analgesic strong enough for the pain expected or the pain being 
experienced? 

Is the timing of drug administration appropriate for the pain expected or 
experienced? 

Is the route of administration appropriate for the child? 

Is the child adequately monitored for the occurrence of side effects? 

Are side effects appropriately managed? 

Has the analgesic regimen provided adequate comfort and satisfaction from 
the perspective of the child or parent(s)? 

Nonpharmacologic strategies 

Have the child and parent(s) been asked about their experience with and 
preferences for a given strategy? 

Is the strategy appropriate for the child's developmental level, condition, and 
type of pain? 

Is the timing of the strategy sufficient to optimize its effects? 

Is the strategy adequately effective in preventing or alleviating the child's pain? 

Are the child and parent(s) satisfied with the strategy for prevention or 
relief of pain? 

Are the treatable sources of emotional distress for the child being addressed? 



pharmacologic research is often limited to single-dose studies in young 
or middle-aged adults and does not assess the complications and side 
effects of medications in the elderly. Elderly patients who participate 
in pain clinics or studies are likely to be the mobile elderly. Further- 
more, elderly patients are often excluded from rehabilitation 
programs and aggressive treatment of pain (Middaugh, Levin, Kee, et 
al., 1988; Sorkin, Rudy, Hanlon, et al., 1990). 

In spite of the lack of research, there is evidence that the elderly 
experience more pain than younger people. It has been estimated that 
the prevalence of pain in those older than 60 years of age (250 per 
1,000) is double that in those younger than 60 (125 per 1,000) (Crook, 
Rideout, and Browne, 1984). Among the institutionalized elderly, the 

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Pain in Special Populations 

prevalence of pain may be over 70 percent (Ferrell, Ferrell, and 
Osterweil, 1990). Elderly patients with cancer often have other 
chronic diseases, more than one source of pain, and complex medica- 
tion regimens that place them at increased risk for drug-drug as well 
as drug-disease interactions. 

Cognitive impairment, delirium (common among the acutely ill 
elderly), and dementia (which occurs in as many as 50 percent of the 
institutionalized elderly) pose serious barriers to pain assessment 
(Kane, Ouslander, and Abrass, 1989). Psychometric properties of pain 
assessment instruments, such as VAS, verbal descriptor, and numerical 
scales, have not been established in this population. Moreover, a high 
prevalence of visual, hearing, and motor impairments in the elderly 
impede the use of these tools. Research on the nursing home popula- 
tion shows that many patients with mild to moderate cognitive impair- 
ment are able to report pain reliably at the moment or when prompted, 
although their pain recall may be less reliable. These findings suggest 
that this population may require more frequent pain assessment than 
patients who are not cognitively impaired (Ferrell, in press). 

Nonopioid analgesics, including acetaminophen and other 
NSAIDs, are helpful adjuncts to opioids for cancer-related pain. The 
risk for gastric and renal toxicity from NSAIDs is increased among 
elderly patients, however, and unusual drug reactions including cogni- 
tive impairment, constipation, and headache are also more common 
(Roth, 1989). Factors that may contribute to altered side effects in the 
elderly include multiple medical diagnoses, multiple drug interactions, 
and altered pharmacokinetics. If gastric ulceration is a concern, 
NSAIDs with lower gastric toxicity (e.g., choline magnesium trisalicy- 
late) should be chosen. The coadministration of misoprostol should 
also be considered as a way to protect the gastric mucosa. 

Opioids are effective for the management of cancer pain in most 
elderly patients. In the elderly, Cheyne-Stokes respiratory patterns are 
not unusual during sleep and need not prompt the discontinuation of 
opioid analgesia. Elderly people tend to be more sensitive to the 
analgesic effects of opioids, experiencing higher peak effect and 
longer duration of pain relief (Kaiko, 1980). The elderly, especially 
those who are opioid naive, also tend to be more sensitive to sedation 
and respiratory depression, probably as a result of alterations in 
metabolism and in the distribution and excretion of the drugs. For this 
reason, the prolonged use of longer acting drugs such as methadone 
requires caution (Ferrell, 1991). 

Elderly people in general have increased fat-to-lean body mass 
ratios and reduced glomerular filtration rates. Opioids produce cogni- 
tive and neuropsychiatric dysfunction through poorly defined mecha- 
nisms that in part include the accumulation of biologically active 
metabolites such as morphine-6-glucuronide or normeperidine 

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Management of Cancer Pain 

(Melzack, 1990). Opioid dosage titration should take into account not 
only analgesic effects but also side effects that extend beyond cogni- 
tive impairment. Such side effects may include urinary retention (a 
threat in elderly males with prostatic hyperplasia), constipation and 
intestinal obstruction, or respiratory depression. 

Local anesthetic infusions, including lidocaine or opioids, may 
result in cognitive impairment if significant drug levels in the blood 
are reached. Orthostatic hypotension and clumsiness may result from 
tricyclic antidepressant administration and other medications used 
for pain management and concurrent medical illnesses. Precautions, 
such as assistance during ambulation, should be taken to prevent 
falls and fractures. 

PCA was shown to be safe and effective for postoperative pain 
relief among some elderly patients (Egbert, Parks, Short, et al., 1990). 
PCA has not been extensively studied for long-term use in the elderly 
with cancer-related pain. The use of any "high-tech" pain treatment 
such as PCA or intraspinal analgesia should be titrated and monitored 
especially closely because of the elderly patient's increased sensitivity 
to drug effects (Ferrell, Cronin Nash, and Warfield, 1992). 

Patients With Psychiatric Problems Associated 
With Cancer Pain 

Although patients with cancer and cancer-related pain commonly 
experience troublesome negative psychological consequences 
(Chapter 1), some patients require treatment beyond that provided by 
the patient's usual health care team. Three cancer centers (Derogatis, 
Morrow, Fetting, et al., 1983) reported that 53 percent of the patients 
were adjusting to the stresses of cancer with no diagnosable psychiatric 
disorder but that the remainder had clinically apparent psychiatric 
disorders. This study also noted that patients with pain were more 
likely to develop a psychiatric disorder; 39 percent of patients with a 
psychiatric diagnosis reported significant pain, but only 19 percent of 
patients without a psychiatric diagnosis had significant pain. 

The incidence of pain, depression, and delirium all increase with 
higher levels of physical debilitation and advanced illness (Burkberg, 
Penman, and Holland, 1984). Approximately 25 percent of all patients 
with cancer experience severe depressive symptoms, with the preva- 
lence increasing to 77 percent in those with advanced illness (Burk- 
berg, Penman, and Holland, 1984). Among patients with cancer, the 
prevalence of organic mental disorders (delirium) requiring psychi- 
atric consultation has been found to range from 25 to 40 percent and 
to rise to as high as 85 percent during the terminal stages of illness 
(Massie, Holland, and Glass, 1983). 

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Pain in Special Populations 

Psychiatric symptoms in patients with pain should be viewed 
initially as a possible consequence of uncontrolled pain. Mood as well 
as personality characteristics may be distorted by the presence of 
uncontrolled pain, and relief of pain may result in the disappearance 
of a perceived psychiatric disorder (i.e., anxiety or depression) (Ahles, 
Blanchard, and Ruckdeschel, 1983). The patient's mental status 
should be reassessed after pain has been controlled to determine if a 
psychiatric disorder is present. The management of specific disorders 
such as depression, delirium, and anxiety in patients with cancer has 
been reviewed in detail elsewhere (Breitbart and Holland, 1988; 
Holland and Rowland, 1989). 

Depression in Patients With Cancer Pain 



The somatic symptoms of depression (e.g., anorexia, insomnia, 
fatigue, and weight loss) are less reliable and lack specificity in the 
patient with cancer (Endicott, 1984). Of greater diagnostic value are 
the psychological symptoms of depression: dysphoric mood, hopeless- 
ness, worthlessness, guilt, and suicidal ideation (Massie and Holland, 
1990). A history of familial depression or of previous depressive 
episodes makes this diagnosis more probable. 

An evaluation of cancer treatment-related organic factors that can 
present as depression should accompany treatment. Such factors 
include corticosteroids (Stiefel, Breitbart, and Holland, 1989), 
chemotherapeutic agents (Adams, Quesada, and Gutterman, 1984), 
whole-brain radiation (DeAngelis, Delattre, and Posner, 1989), CNS 
metabolic-endocrine complications (Breitbart, 1989), and paraneo- 
plastic syndromes (Patchell and Posner, 1989). 

Depressed patients with cancer are usually treated with supportive 
psychotherapy, cognitive-behavioral techniques, and antidepressant 
medications (Massie and Holland, 1990). The efficacy of tricyclic and 
other antidepressants in cancer patients is well established (Popkin, 
Callies, and Mackenzie, 1985). Psychostimulants are most helpful in 
the treatment of depression in patients with advanced disease and in 
those for whom dysphoric mood is associated with severe psychomo- 
tor slowing and even mild cognitive impairment. Clinicians are 
referred to the guideline on treatment of depression for further infor- 
mation on this subject (Depression Guideline Panel, 1993a, 1993b). 

A patient's use of meperidine while on a monoamine oxidase 
inhibitor (MAOI) is absolutely contraindicated because it can lead to 
hyperpyrexia and cardiovascular collapse. One should be extremely 
cautious when using any opioid analgesics in patients on MAOIs, 
because myoclonus and delirium have been reported (Breitbart and 
Holland, 1988). Sympathomimetic drugs and other less obvious 
MAOIs, such as the chemotherapeutic agent procarbazine, can cause 

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Management of Cancer Pain 

Table 23. Risk factors that predispose cancer patients 
to depressive disorders 

Social isolation. 
Recent losses. 
A tendency to pessimism. 
Socioeconomic pressures. 
A history of mood disorders. 
Alcohol or substance abuse. 
Previous suicide attempt(s). 
Poorly controlled pain. 

Source: Depression Guideline Panel, 1993a. 



a hypertensive crisis in patients taking an MAOI. If a patient has 
responded well to an MAOI for depression in the past, its continued 
use is warranted, but with caution. 

Suicide and Cancer Pain 



Few patients with cancer commit suicide, but poorly controlled 
pain places them at increased risk. Tables 23 and 24 list factors that 
predispose cancer patients to depression and increase risk of suicide. 

Although fleeting or occasional thoughts of suicide probably occur 
commonly in those with advanced illness, persistent and intense 
suicide thinking is rare in the absence of depression or of uncontrolled 
physical symptoms such as pain (Breitbart, 1990a). Suicide is often 
held as an option by the patient to retain a sense of control. Fear of 
unacceptable pain was a major component of requests to physicians 
for assisted death (Helig, 1988) and is so important to patients with 
cancer that 69 percent reported that they would consider committing 
suicide if their pain was not adequately treated (Levin, Cleeland, and 
Dar, 1985). In another study, the majority of patients who committed 
suicide had severe pain that was inadequately controlled (Bolund, 
1985). Clinicians in a pain clinic report seeing many patients who 
considered suicide who changed their minds once given adequate pain 
relief (Foley, 1991). For at-risk patients, clinicians should be aggres- 
sive in the use of analgesics and other appropriate drugs as well as 

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Pain in Special Populations 

Table 24. Suicide risk factors in cancer patients with pain 

Depression. 

Poorly controlled pain. 

Previous suicide attempt(s). 

Family history of suicide. 

Delirium. 

Substance abuse. 

Prior psychiatric diagnosis (depression). 

Advanced disease. 

Increasing age. 

Disfiguring disease or surgery. 

Poor social support. 

Source: Depression Guideline Panel, 1993a. 



crisis intervention-oriented psychotherapeutic approaches that mobi- 
lize the patient's support system. 

Although it is appropriate to intervene when medical or psychiatric 
factors are clearly the driving force in a suicidal cancer patient, overly 
aggressive intervention may be less helpful in patients with advanced 
illness when comfort and symptom management are the primary 
concerns. As an alternative to suicide, the goal of intervention should 
be to establish rapport, to develop an alliance, and to provide effective 
management of symptoms. 



Anxiety. 



Although the experience of anxiety is a normal response when 
people learn they have cancer or in the case of recurrence or treat- 
ment failure, patients who continue to experience high levels of anxi- 
ety for weeks or months should be referred to a psychiatrist, psycholo- 
gist, psychiatric nurse, or psychiatric social worker for evaluation and 
possible treatment. Some patients with cancer have long-standing or 
chronic anxiety disorders, such as phobias and panic disorder, that can 
be exacerbated by the stressors of cancer illness or treatment. Claus- 
trophobic patients may experience acute anxiety when confined in 
diagnostic scanning devices or radiotherapy treatment rooms (Bren- 
nan, Redd, Jacobsen, et al., 1988). Patients who experience such acute 
anxiety or exacerbations of chronic anxiety disorders may require the 

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Management of Cancer Pain 

use of medications such as benzodiazepines or cognitive-behavioral 
therapies to help them tolerate procedures. 

Delirium and Its Effects on Treating Pain 



Cognitive failure (delirium), common in patients with advanced 
illness (Fleishman and Lesko, 1989), is an etiologically nonspecific, 
global, cerebral dysfunction, characterized by concurrent disturbances 
of level of consciousness, attention, thinking, perception, memory, 
psychomotor behavior, emotion, and the sleep-wake cycle. Disorienta- 
tion, fluctuation, waxing and waning of the above symptoms, and 
acute or abrupt onset of such disturbances are other critical features 
of delirium. Delirium is reversible, even in advanced illness. Still, it 
may not be reversible in the last 24 to 48 hours of life, most likely 
because of irreversible processes such as multiple organ failure 
(Massie and Holland, 1990). 

At times, it is difficult to differentiate delirium from dementia 
because they frequently share clinical features such as disorientation 
and impaired memory, thinking, and judgment. One difference is that 
the temporal onset of symptoms is more subacute or chronically pro- 
gressive in dementia than in delirium. Occasionally, delirium is super- 
imposed on an underlying dementia, such as in the case of an elderly 
patient, an AIDS patient, or a patient with a paraneoplastic syndrome. 

Delirium can be due to the direct effects of cancer on the CNS, to 
indirect CNS effects of the disease or treatments (medications, elec- 
trolyte imbalance, failure of a vital organ or system, infection, vascular 
complications) and to preexisting cognitive impairment or dementia. 

Medical and nursing staff sometimes conclude that a new symp- 
tom is psychologically based without first ruling out all possible 
organic causes. Given the many drugs that cancer patients require and 
the fragile state of their physiologic functioning, even routinely 
ordered hypnotics can be enough to precipitate delirium. Opioid anal- 
gesics, including levorphanol, morphine sulfate, methadone, and 
meperidine (Bruera, Macmillan, Hanson, et al., 1989), can cause 
confusional states, particularly in the elderly and terminally ill. Clini- 
cians should correct those underlying causes of delirium (Adams, 
Fernandez, and Andersson, 1986; Fainsinger and Bruera, 1992; Fish, 
1991; Lesko and Fleishman, 1991; Lipowski, 1987). 

Substance Abusers 

There is a low risk of iatrogenic addiction in patients with cancer 
(Kanner and Foley, 1981). For patients with cancer who are addition- 
ally diagnosed as substance abusers, the complex physiologic, behav- 
ioral, and psychological phenomena associated with drug addiction in 

134 



Pain in Special Populations 

no way exclude the ability to perceive painful stimuli. When opioids 
are required for pain management, the concurrence of substance abuse 
disorders and cancer produces a difficult and stressful situation for 
even the most experienced clinician. Nevertheless, certain principles 
can be followed to assure a careful and fair assessment of the pain 
complaint and to provide the best chance of achieving satisfactory pain 
relief in these circumstances (Portenoy and Payne, 1992). These princi- 
ples are complementary to those discussed elsewhere in this guideline. 

Tolerance and physical dependence are predictable consequences 
of chronic opioid use, but they do not equal addiction (Newman, 
1983). Numerous clinical, epidemiologic, and pharmacologic studies 
now suggest that cancer patients may become tolerant and physically 
dependent on opioids if therapeutic doses are prescribed for several 
weeks. However, very few patients develop the loss of control and 
compulsive use patterns that characterizes addiction to opioids (and 
other prescribed or illicit substances) despite medical, social, legal, or 
emotional harm. This sort of behavior, more than tolerance and physi- 
cal dependence, characterizes and defines addiction (Portenoy and 
Payne, 1992). 

An adequate assessment of the cause of pain is essential to the 
optimal treatment of the opioid addict with cancer. As with other 
cancer populations, specific antitumor treatments are indicated as the 
single best method of pain relief. Frequently, however, adequate anal- 
gesia has to be established before diagnostic studies and medical or 
surgical treatments can proceed. The appropriate management of the 
medical condition often decreases the requirements for opioids. 
Optimal pain treatment is essential to preventing the syndrome of 
"pseudoaddiction" (Weissman and Haddox, 1989) because inadequate 
pain management will invariably produce the manipulative behavior 
that the clinician wants to avoid. 

Although not clearly substantiated by prospective clinical studies, 
it is common practice to make distinctions among (1) addicts who are 
actively abusing opioids and illicit narcotics at the time of their treat- 
ment for acute pain, (2) former addicts who no longer abuse drugs, 
and (3) addicts in methadone maintenance (Fultz and Sonay, 1975). 
Patients actively abusing heroin or prescription opioids (and those on 
methadone maintenance) should be assumed to have some degree of 
pharmacologic tolerance, which will be reflected in a need for higher- 
than-usual starting doses and dosing intervals shorter than those 
generally recommended in the nonaddicted population. Furthermore, 
because patients who are actively abusing drugs often manifest 
psychological disorders that influence pain perception (e.g., anxiety 
and depression), the treatment of concomitant psychiatric distur- 
bances is often necessary and usually requires the consultation of 
experienced psychiatric clinicians. Patients with cancer who have 

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Management of Cancer Pain 

abused drugs in the past (but who are not current abusers) or who are 
participating in methadone maintenance programs may have a higher 
degree of opioid tolerance than the general population. Among these 
patients, it is useful to anticipate that significant anxiety may accom- 
pany the stress of medical illness and acute pain and be manifested in 
a reappearance of drug-abuse behaviors. 

The use of opioid agonist-antagonist compounds in known or 
suspected active opioid addicts is absolutely contraindicated. Not only 
do these drugs have ceiling effects to their analgesic efficacy, and are 
therefore inappropriate for severe pain, but they may also precipitate 
withdrawal and increased pain in physically dependent patients. Like- 
wise, nonopioid analgesic modalities should not be substituted for 
opioid analgesics to treat severe pain in patients who are suspected or 
known abusers of illicit substances. Tolerance to opioid analgesics 
decreases the duration of effective analgesia (Houde, 1979); therefore, 
"tolerant" patients require more frequent dosing than do nontolerant 
patients. For example, morphine, which has an average analgesic 
duration of 3 to 4 hours, may produce only 1 to 2 hours of pain relief 
in an opioid addict with a large degree of tolerance. 

Paradoxically, PCAs are being used with increasing frequency when 
rapid titration of intravenously administered opioids is required in this 
population. Although it would seem that the administration of opioids 
could not be entrusted to an addicted individual, in fact, it has its advan- 
tages: With the appropriate prescription of doses, "lock-out" intervals, 
and instruction to the patient, this method of administration may reduce 
the confrontation and conflict inherent in clinician-administered 
analgesia. Opioid addicts may report a euphoric feeling or "high" coin- 
cident with an intravenous bolus injection of opioids, which presum- 
ably reinforces the need to self-administer drugs (Jaffe, 1985). Never- 
theless, intravenous opioids can be used effectively (see below). 

Appropriate PCA bolus doses and "lock-out" periods (i.e., the 
time that should elapse between the administration of one dose and 
the next) should be selected. The opioid addict may be easily under- 
dosed and experience poor pain relief if the degree of the patient's 
tolerance is not accurately assessed. The commonly published "lock- 
out" times and starting bolus doses are inappropriate for most opioid 
addicts and indeed for many patients whose prior opioid experience is 
such that they manifest opioid tolerance; in fact, the typical published 
parameters apply to the postoperative population of relatively opioid- 
naive patients. The prolonged self-administration of morphine to 
cancer patients with acute recurrent pain caused by oral mucositis 
after bone marrow transplantation did not increase the risk for over- 
medication or addiction (Chapman and Hill, 1989), and compared 
with standard intravenous infusion, PCA decreased the requirements 
for morphine by 53 percent (Hill, Chapman, Kornell, et al., 1990). 

136 



Pain in Special Populations 

Although those patients were not addicts, the data nevertheless 
support the argument that PC A of intravenous morphine for pain 
does not invariably lead to ever-escalating dose requests. 

Patients who are maintained on methadone for the treatment of 
addiction may also be treated with this agent for pain, if it is adminis- 
tered frequently enough. In this setting, methadone is useful in that 
the patient's dose may be easily tapered back to the level of the main- 
tenance dose after the painful episode has been treated. In reality, 
however, most methadone maintenance programs do not have the 
flexibility to change the rules for individual patients to allow increases 
in the daily methadone dose or to increase the dosing frequency 
beyond once or twice a day. Unfortunately, then, the treatment of pain 
with methadone in this manner usually has to take place outside of the 
typical maintenance program. 

For acute focal pain syndromes, regional anesthetic approaches 
such as somatic and sympathetic nerve block should be considered, 
unless contraindicated. These approaches are generally unsafe in 
patients who are septic, who have coagulopathy, or who are acutely 
confused and uncooperative. Nonpharmacologic methods can be 
useful adjuncts in the treatment of pain in this population. 

One common characteristic of patients who are actively abusing 
opioids is a failure to set limits on their drug-seeking behavior, even in 
the presence of liberal uses of opioids for pain management. The clini- 
cian should discuss expectations and define limits of acceptable and 
unacceptable behaviors with the patient. The use of drug infusion 
pumps with security locks (available on almost all PCA pumps) 
should prevent dose escalation beyond what the clinician prescribes. 
If oral opioid analgesics are being administered, patients should be 
told that their ingestion will be witnessed and that routine precau- 
tions, such as searching the room for hidden pills or signs of hoarding, 
will be taken. 

In the outpatient setting, clearly stated, written rules should cover 
prescription renewals, the procedure to be followed with lost or stolen 
prescriptions or medications, and procedures to ensure that only one 
clinician is prescribing analgesic medications. Prescription theft or 
forgery should lead either to the patient's admission to the hospital for 
continuation of opioid therapy, if still required, or to withdrawal of the 
therapy and referral to an appropriate drug treatment program, if 
opioid therapy for pain is no longer required. The patient should be 
seen frequently — daily, if necessary — and a limited quantity of opioids 
should be prescribed. In some States, the prescription of opioids to a 
patient known to be a "habitual user" or "addict" must be reported to 
the State's regulatory agencies. 

These general guidelines allow the clinician and the patient to 
establish behavioral expectations, which may be the only way to 

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Management of Cancer Pain 

manage humanely. Patients with pain and substance abuse disorders 
require interdisciplinary assessment and care. These patients are 
generally not well managed by the traditional medical models of onco- 
logic care, because the issues of pain management and substance 
abuse treatment together are almost always beyond the competence 
of a single clinician or clinical service and may often produce directly 
conflicting goals for treatment. On the one hand, for example, the 
traditional method of opioid addiction treatment is to detoxify the 
patient and provide pharmacologic and psychological therapies to 
maintain abstinence. On the other hand, in treating the addict with 
cancer-related pain, the avoidance of opioids is usually unacceptable, 
because there are few alternatives for effective pain treatment. 
However, the pain specialist usually has little ability or training to 
assess fully the behaviors manifested by addicts, particularly those 
actively abusing drugs. There is no obvious solution to this paradox, 
but clearly, clinical research is needed to develop a model for the care 
of the addict with pain that allows flexibility of traditional concepts of 
substance abuse and pain management and provides a mechanism that 
effectively integrates both disciplines. 

Minority Populations 

In general, minority patients are likely to receive less adequate 
cancer treatment (Blendon, Aiken, Freeman, et al., 1989; Freeman 
and Wasfie, 1989). Indexing the adequacy of cancer pain management 
by WHO standards, a recent multicenter study found that minority 
patients (African- Americans and Hispanics) with pain due to metasta- 
tic cancer were three times more likely to have inadequate pain treat- 
ment than those seen in nonminority settings (Cleeland, Gonin, 
Hatfield, et al., in press). 

The barriers that limit pain control in nonminority patients are 
even more likely to impede the pain management of minority patients. 
Cultural and linguistic differences may impair adequate assessment. 
Less frequent followup care will also lead to less adequate identifica- 
tion and monitoring of pain. Health care providers may be more 
concerned about the potential addiction of minority patients who need 
opioid medications on a chronic basis, and many minority patients may 
be more reluctant to use analgesics they see as potentially addicting. 
Because of concerns about theft and violence, pharmacies in neighbor- 
hoods where minorities live may not stock opioid analgesics (Kanner 
and Portenoy, 1986). Minority patients are more often economically 
disadvantaged, leading to inadequate reimbursement for pain control. 
Patients and families may face the dilemma of choosing between 
paying for pain medications or paying for other necessities. 

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Pain in Special Populations 

Patients from special populations, because of their behavior when 
they have pain, may also be perceived as needing less aggressive pain 
management. Health care professionals frequently comment that such 
patients seem to have less pain even when they have equally severe 
tissue damage, because pain in these patients is inadequately assessed, 
but patients from diverse cultural and linguistic backgrounds will rate 
their pain at a similar level of severity when given the appropriate 
pain rating scales (Cleeland, 1989a). Judging pain by just observing 
the behavior of the patient will lead to consistent underestimation of 
its severity (Grossman, Sheidler, Swedeen, et al., 1991). Therefore, 
when developing a pain treatment plan, health care clinicians should 
be aware of the unique needs and circumstances of patients from vari- 
ous ethnic and cultural backgrounds. 

Pain in Patients With AIDS 

Pain is a symptom commonly experienced by patients with HIV 
infection, even in the absence of an opportunistic cancer such as 
Kaposi's sarcoma (O'Neill and Sherrard, 1993). The principles of pain 
assessment and treatment in the patient with HIV positive /AIDS are 
not fundamentally different from those in the patient with cancer and 
should be followed for patients with HIV positive /AIDS. 

The reported prevalence of pain in HIV-infected individuals varies 
depending on stage of disease, care setting, and study methods. Esti- 
mates of the prevalence of pain in HIV-infected individuals generally 
range from 40 to 60 percent with prevalence of pain increasing as 
disease progresses (Breitbart, Passik, Bronaugh, et al., 1991; Lebovits, 
Lefkowitz, McCarthy, et al., 1989; Schofferman and Brody, 1990; Singer, 
Zorilla, Fahy-Chandon, et al., 1993). Thirty-eight percent of ambulatory 
HIV-infected patients reported significant pain in a prospective study of 
current pain prevalence (Breitbart, Passik, Bronaugh, et al., 1991). Fifty 
percent of patients with AIDS reported pain, while 25 percent of those 
with earliest stages of HIV infection had pain. Patients had an average 
of pain from two or more sources at a time. A review of ambulatory 
HIV-infected men (Singer, Zorilla, Fahy-Chandon, et al., 1993) demon- 
strated that 28 percent of those who were asymptomatic seropositive, 
55.6 percent of those with AIDS-related complex, and 80 percent of 
those with AIDS reported one or more painful symptoms over a 6- 
month period. A study of pain in hospitalized patients with AIDS 
revealed that over 50 percent of patients required treatment for pain 
with pain the presenting complaint in 30 percent (Lebovits, Lefkowitz, 
McCarthy, et al., 1989). Schofferman and Brody (1990) reported that 53 
percent of patients with far-advanced AIDS cared for in a hospice 
setting had pain. The most common pain syndromes reported in 
studies to date include painful peripheral sensory neuropathy, pain 

139 



Management of Cancer Pain . 

from extensive Kaposi's sarcoma, headache, pharyngeal and abdomi- 
nal pain, arthralgias and myalgias, and painful dermatologic condi- 
tions (Breitbart, Passik, Bronaugh, et al., 1991; Lebovits, Lefkowitz, 
McCarthy, et al., 1989; Schofferman and Brody, 1990; Singer, Zorilla, 
Fahy-Chandon, et al, 1993). 

HIV-related peripheral neuropathy is often a painful condition, 
affecting up to 30 percent of people with AIDS (Cornblath and 
Mc Arthur, 1988), and is characterized by a sensation of burning, 
numbness, or anesthesia in the affected extremity. Several antiviral 
drugs, such as didanosine or zalcitabine, chemotherapy agents used to 
treat Kaposi's sarcoma (vincristine), as well as phenytoin and isoni- 
azid, can also cause painful peripheral neuropathy. 

Reiter's syndrome, reactive arthritis, and polymyositis are painful 
conditions reported in early HIV infection (Kaye, 1989). Other painful 
rheumatologic manifestations of HIV infection include various forms of 
arthritis (painful articular syndrome, septic arthritis, psoriatic arthritis), 
vasculitis, Sjogren's syndrome, polymyositis, zidovudine (AZT) myopa- 
thy, and dermatomyositis (Espinoza, Aguilar, Berman, et al., 1989). 

Conditions associated with chronic or intermittent pain include 
intestinal infections with Mycobacterium avium-intracellular e and 
Cryptosporidium, which cause cramping and intermittent abdominal 
pain; hepatosplenomegaly, resulting in abdominal distention and pain; 
oral and esophageal candidiasis, causing pain while the patient is 
eating and swallowing; and severe spasticity associated with 
encephalopathy, which causes painful muscle spasms. 

HIV-related conditions that cause acute pain in children include 
meningitis and sinusitis, which result in severe headaches; otitis 
media; shingles; cellulitis and abscesses; severe Candida dermatitis; 
and dental caries. 

The patient with HIV disease faces many stressors during the 
course of illness including dependency, disability, and fear of pain and 
painful death. Such concerns are universal; the level of psychological 
distress, however, is variable and depends on social support, individual 
coping capacities, personality, and medical factors, such as the extent 
or stage of illness. In a study of pain in ambulatory HIV-infected 
patients (Breitbart, 1993), depression was significantly correlated with 
the presence of pain. In addition to being significantly more distressed 
and depressed, those with pain (40 percent) were twice as likely to 
have suicidal ideation as those without pain (20 percent). HIV- 
infected patients with pain were more functionally impaired, were 
more depressed, were more likely to be unemployed or disabled, and 
reported less social support. 

Children with HIV infection often come from multiproblem fami- 
lies (Boland, Mahan-Rudolph, and Evans, 1989). Many families have 
more than one infected member, and multiple losses from AIDS in 

140 



Pain in Special Populations 

one family are common. These issues affect how families deal with the 
disease and the pain it causes. Parental guilt, which often results in 
denial of the disease, can also cause denial of a child's pain and resis- 
tance to adequate pain management. 

Fears of addiction and concerns regarding drug abuse affect both 
patient compliance and clinician management of opioid analgesics and 
often lead to the undermedication of HIV-infected patients in pain. 
Also problematic is the management of pain in the growing segment 
of HIV-infected people who are actively using illicit drugs. 

The issue of drug abuse is also problematic in the pediatric HIV 
population. Many children with HIV infection live in families where 
intravenous drug abuse is or was a problem. Either they have parents 
who are actively using drugs or are recovered from drug abuse, or 
they live with extended family who have had experiences with their 
drug-abusing relatives. In these environments, questions arise about 
the safety of prescribing opioids for the child. Extended-family 
members are often anxious about the use of opioids for a child whose 
parent was a drug addict, fearing that the child will also become 
addicted. These fears and concerns should be anticipated and 
discussed, and explicit plans such as those discussed earlier should be 
put into place to minimize the risk of drug diversion. 

The general management of pain in children with HIV is the 
same as that for children with cancer. The assessment of pain in 
HIV-infected children may be complicated by the frequency of 
encephalopathy and related developmental delays. It is often difficult 
to determine whether an encephalopathic infant or toddler who 
cannot talk is in pain. Observations of a child's response to a trial of 
pain medication may be the best means of assessing such a child's pain 
(see Chapter 6). 



141 



8 



Monitoring the Quality of 
Pain Management 



Recommendations 

63. To assure optimal pain management, formal means should be 
developed and used within each institution for evaluating pain 
management practices and for obtaining patient feedback to gauge 
the adequacy of its control. The quality of pain management 
should be evaluated in all settings where patients with cancer 
receive care. (C) 

64. The quality of cancer pain management should be evaluated at 
points of transition in the provision of services (e.g., from the 
hospital to the home) to determine that optimal pain management 
is achieved and maintained. (C) 

65. For pain management to be effective, each practice setting should 
designate who will be responsible for pain management. (C) 

66. Policy and standard procedures, which define the acceptable level 
of patient monitoring and appropriate roles and limits of practice 
for health care providers, should govern the use of specialized 
analgesic technologies. (C) 

To ensure optimal pain management, formal means should be 
developed and used within each institution for evaluating cancer pain 
management practices (American Pain Society, Committee on Quality 
Assurance Standards, 1990; National Institutes of Health Consensus 
Development Conference, 1987) and should include feedback regard- 
ing the adequacy of pain relief. Optimal pain management requires 
the interaction of all members of the health care team including the 
patient. A formal process should be developed to evaluate the quality 
of pain management across all stages of the disease and across all 
practice settings. 

Quality pain management begins with an affirmation by health 
care professionals that patients should have access to the best level of 
pain relief that can safely be provided. In any setting, the quality of 
pain control is influenced by the training, expertise, and experience of 
clinicians. Practice settings vary considerably in size, complexity, 
resources, and patient populations. In addition, the goals of pain 
management may differ depending on the cause of the pain and the 
stage of the disease. Different pain management programs are there- 
fore suitable in different practice settings, but the responsibility for 
pain management should always be assigned to the clinicians most 

143 



Management of Cancer Pain , 

knowledgeable, experienced, interested, and available to respond to 
patients' needs quickly. 

One aspect of pain management that should be considered when 
evaluating quality of care is the multiplicity of settings where cancer 
care is provided. Patients with cancer receive care in ambulatory care 
centers, clinicians' offices, hospitals, their own homes, nursing homes, 
and hospices. Pain management should be evaluated at points of tran- 
sition in the provision of services to ensure that optimal pain manage- 
ment is achieved and maintained. 

The key items to consider when developing a formal program to 
monitor the provision of pain relief are: 

■ Patients' satisfaction with pain management and its impact on 
their quality of life. 

■ Family satisfaction with pain management and its impact on their 
quality of life. 

■ The designation of who is responsible for pain management. 

■ The systematic assessment of cancer-related pain in all settings 
where patients receive care. 

■ The accuracy of diagnostic approaches for common cancer pain 
syndromes. 

■ The range and appropriateness of pain management options avail- 
able within a particular practice setting. 

■ The effectiveness of pain management options utilized to prevent 
and treat pain. 

■ The prevalence and severity of side effects and complications 
associated with pain management. 

■ The quality of pain management across points of transition in the 
provision of services (American Pain Society, 1992; Miaskowski 
and Donovan, 1992; Miaskowski, Jacox, Hester, et al., 1992). 

The implementation of this guideline requires collaboration across 
disciplines and among clinicians. Three elements are essential for 
interdisciplinary collaboration: A common purpose, diverse profes- 
sional skills and contributions, and effective communication and coor- 
dination of services (Spross, 1989). The common purpose is the relief 
of the patient's pain. To meet this goal, the diverse and complemen- 
tary skills and contributions of each health care professional should be 
recognized and used. At times, however, interpersonal issues of 
power, leadership, and conflict can hamper efforts to relieve pain. 
Competent leadership and attention to conflict resolution are vital for 
building teams and keeping them focused on their shared purpose. 

144 



Monitoring Quality of Pain Management 

The following elements will help ensure effective communication 
and collaboration: 

■ Clarity among professionals about what they can and will 
contribute (e.g., who will coordinate pain management — the 
primary nurse and attending physician or a specialized pain 
control team? Can consultants write prescriptions or orders?). 

■ Decision making that reflects the input and preferences of the 
patient and family, such as providing a number of pain control 
choices that include pharmacologic and nonpharmacologic options. 

■ Contingency planning, including orders to avert or treat possible 
side effects; a range of analgesic doses to deal with varying pain 
intensity; ongoing followup of cancer-related pain problems; and 
clear directions about whom the patient or caregiver should notify 
if changes in the plan are required. 

■ In institutional settings, regular interdisciplinary meetings of clini- 
cians to maximize communication and information sharing and to 
ensure appropriate planning. 

The following recommendations (adapted from American Pain 
Society, 1992) should be implemented in every practice setting where 
patients with cancer receive care: 

1. Promise patients attentive care. Patients should be informed, 
orally and in writing, that effective pain management is an impor- 
tant part of their treatment, that talking about unrelieved pain is 
important, and that health care professionals will respond quickly 
to reports of pain. It should be made clear to patients and families, 
however, that the total absence of any discomfort is not always an 
achievable goal. 

2. Assign responsibility for pain management to clinicians most 
knowledgeable, experienced, interested, and able to respond to 
patients' needs in a timely fashion. 

3. Document the assessment of pain and its relief An assessment of 
pain intensity and pain relief should be recorded, regularly 
reviewed by members of the health care team, and incorporated 
into the patient's permanent record. The intensity of pain should 
be assessed and documented regularly (depending on the severity 
of pain) and with each new report of pain. The degree of pain 
relief should be determined after each intervention, once a suffi- 
cient time has elapsed for the treatment to reach peak effect. A 
simple, valid measure of intensity and relief should be selected, 
and the patient and family should be instructed in the use of the 
tool. For children, age-appropriate measures should be used (see 
Chapters 2 and 7). 

145 



Management of Cancer Pain 

4. Define pain and relief levels to trigger a review. Each practice 
setting should identify values for rating pain intensity and pain 
relief that will elicit a review of the current pain therapy. The 
proposed modifications in treatment should be documented, and 
the effectiveness of the modified treatment should be reviewed 
subsequently. Cleeland, for example, has shown that when patients 
indicate a level of "5" or above on a scale from to 10, the 
patient's ability to function is markedly affected (Cleeland, 1984). 

5. Survey patient satisfaction. At regular intervals, as defined by the 
practice setting and the quality improvement committee (if avail- 
able), each setting should assess a randomly selected sample of 
cancer patients who have pain. Patients should be asked to rate 
their current pain intensity, the worst pain intensity in the past 24 
hours, the degree of relief obtained from interventions, side effects 
associated with pain management, satisfaction with relief, satisfac- 
tion with the responsiveness of clinicians, and the extent to which 
their preferences in pain management were taken into account. 

6. Analgesic drug treatment should comply with two basic principles: 

■ Oral analgesics and other noninvasive routes of administration are 
used whenever possible and administered in accordance with the 
principles expressed in the WHO analgesic ladder. 

■ Analgesics are titrated to maximally effective doses or the appear- 
ance of dose-limiting side effects before specialized invasive anal- 
gesic approaches are used. 

7. Monitor use of specialized analgesic technologies. The adminis- 
tration of intraspinal opioids, systemic or intraspinal PC A, contin- 
uous opioid infusion, local anesthetic infusion, and conscious or 
deep sedation should be governed by policy and standard proce- 
dures that define the acceptable level of patient monitoring and 
appropriate roles and limits of practice for all health care profes- 
sionals involved. The policy should include definitions of physician 
and nurse accountability, physician and nurse responsibility to the 
patient, and the role of the pharmacist. 

8. Offer nonpharmacologic interventions. Physical modalities and 
cognitive- and behavior-based interventions can provide substan- 
tial pain relief. Such interventions generally should be used to 
supplement, not replace, pharmacologic interventions. 

9. Monitor the efficacy of pain treatment. Periodically review pain 
treatment procedures using the practice setting's quality improve- 
ment mechanisms. 

146 



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182 



Acronyms 



ACS American Cancer Society 

AHCPR Agency for Health Care Policy and Research 

AIDS Acquired immunodeficiency syndrome 

APAP Acetaminophen 

ARS Adjective rating scale 

AZT Zidovudine, commonly referred to as AZT 

CNS Central nervous system 

CSA Controlled Substances Act 

CSF Cerebrospinal fluid 

CT scan Computed tomographic scan 

EMLA : Eutectic mixture of local anesthetic 

FDA Food and Drug Administration 

GI Gastrointestinal 

HIV Human immunodeficiency virus 

MAOI Monamine oxidase inhibitors 

MRI Magnetic resonance imaging 

NRS Numerical rating scale 

NSAID Nonsteroidal anti-inflammatory drug 

PCA Patient-controlled analgesia 

TENS Transcutaneous electrical nerve stimulation 

WHO World Health Organization 

VAS Visual analogue scale 



183 



Glossary 



Ablative surgery. Surgical procedures performed on peripheral 
nerves, the spinal cord, the brain or brain stem that relieve pain by 
permanent disruption of nerve pathways. 

Acupuncture. The piercing of specific body sites with needles to 
produce pain relief. 

Addiction (psychological dependence). Pattern of compulsive drug 
use characterized by a continued craving for an opioid and the need to 
use the opioid for effects other than pain relief. 

Adjuvant analgesic drug. A drug that is not a primary analgesic but 
that research has shown to have independent or additive analgesic 
properties. 

Anxiolysis. Sedation or hypnosis used to reduce anxiety, agitation, or 
tension. 

Anxiolytic. Medication used to reduce anxiety, agitation, or tension. 

Behavioral techniques. A coping strategy in which patients are taught 
to monitor and evaluate their own behavior and to modify their reac- 
tions to pain. 

Biofeedback. A process in which a person learns to influence reliably 
physiologic responses of two kinds: those that are not ordinarily under 
voluntary control or those that ordinarily are easily regulated but for 
which regulation has broken down because of trauma or disease. 

Breakthrough pain. Intermittent exacerbations of pain that can occur 
spontaneously or in relation to specific activity. 

Cognitive reappraisal. A coping strategy in which patients are taught 
to monitor and evaluate negative thoughts and replace them with 
more positive thoughts and images. 

Conscious sedation. "Light sedation" during which the patient retains 
airway reflexes and responses to verbal stimuli. 

Counterstimulation. Application of moderate to intense sensory stimu- 
lation, such as with cold, heat, rubbing, pressure, or electrical current, 
so as to decrease perception of pain at the same or a distant site. 

Cryotherapy. The therapeutic use of cold to reduce discomfort; limit 
progression of tissue edema; or break a cycle of muscle spasm. 
Cryotherapy is a form of counterirritation. 

185 



Management of Cancer Pain 

Deafferentation pain. Pain due to loss of sensory input into the central 
nervous system, as occurs with avulsion of the brachial plexus or other 
types of lesions of peripheral nerves or because of pathology of the 
central nervous system. 

Distraction. The cognitive strategy of focusing attention on stimuli 
other than pain or negative emotions that accompany pain. 

Dysesthesia. An unpleasant abnormal sensation, whether spontaneous 
or evoked. 

Epidural. Situated within the spinal canal, on or outside the dura 
mater (tough membrane surrounding the spinal cord); synonyms are 
"extradural" and "peridural." 

Equianalgesic. Having equal pain-killing effect; morphine sulfate, 10 
mg intramuscularly, is generally used for opioid analgesic compar- 
isons. 

Horner's syndrome. A Pancoast tumor that involves both the upper 
and lower brachial plexus. 

Hyperpathia. A painful syndrome, characterized by increased reaction 
to a stimulus, especially a repetitive stimulus, as well as an increased 
threshold. 

Hypnosis. A state of heightened awareness and focused concentration 
that can be used to manipulate the perception of pain. 

Iatrogenic. Induced inadvertently by the medical treatment or proce- 
dures of a physician. 

Imagery. A cognitive-behavioral strategy that uses mental images as 
an aid to relaxation. 

Incident pain. See "movement-related pain." 

Intrathecal. Within a sheath, e.g., cerebrospinal fluid that is contained 
within the dura mater. 

Lancinating. Characterized by piercing or stabbing sensations. 

Local nerve block. Infiltration of a local anesthetic around a peripheral 
nerve so as to produce anesthesia in the area supplied by the nerve. 

Mixed opioid agonist-antagonist. A compound that has an affinity for 
two or more types of opioid receptors and blocks opioid effects on one 
receptor type while producing opioid effects on a second receptor type. 

Movement-related pain. A type of breakthrough pain that is related to 
specific activity, such as eating, defecation, socializing, or walking. 
Also referred to as incident pain. 

186 



Glossary 

Mucositis. Inflammation of a mucous membrane. Oral mucositis is a 
common complication of chemotherapy and radiation therapy. 

Music therapy. A form of distraction that uses music as an aid to 
relaxation. 

Myofascial pain. A large group of muscle disorders characterized by 
the presence of hypersensitive points, called trigger points, within one 
or more muscles and/or the investing connective tissue together with a 
syndrome of pain, muscle spasm, tenderness, stiffness, limitation of 
motion, weakness, and occasionally autonomic dysfunction. 

Neurolytic block. The injection of a chemical agent to cause destruc- 
tion and consequent prolonged interruption of peripheral somatic or 
sympathetic nerves, or in some cases, the neuraxis. 

Neuropathic pain. Pain that results from a disturbance of function or 
pathologic change in a nerve; in one nerve mononeuropathy; in 
several nerves, mononeuropathy multiplex; if diffuse and bilateral, 
polyneuropathy. 

Nociceptive. The process of pain transmission; usually relating to a 
receptive neuron for painful sensations. 

NSAID. Aspirin-like drug that reduces inflammation (and hence 
pain) arising from injured tissue. 

Opioid agonist. Any morphine-like compound that produces bodily 
effects including pain relief, sedation, constipation, and respiratory 
depression. 

Opioid partial agonist. A compound that has an affinity for and stimu- 
lates physiologic activity at the same cell receptors as opioid agonists 
but that produces only a partial (i.e., submaximal) bodily response. 

Opiate receptor. Opiate-binding sites found throughout primary affer- 
ents and the neuraxis. 

Pain. An unpleasant sensory and emotional experience associated with 
actual or potential tissue damage or described in terms of such damage. 

Palliative therapy. A procedure such as chemotherapy, radiation ther- 
apy, or surgery that is performed to relieve or ease pain. 

Pancoast tumor. Tumor originating from the superior sulcus of the 
lung that invades all or a portion of the brachial plexus. 

PCA. Self-administration of analgesics by a patient instructed in doing 
so; usually refers to self-dosing with intravenous opioid (e.g., 
morphine) administered by means of a programmable pump. 

187 



Management of Cancer Pain 

Physical dependence. Physiologic adaptation of the body to the pres- 
ence of opioid is required to maintain the same level of analgesia. 

Physical modalities. Therapeutic interventions that use physical meth- 
ods, such as heat, cold, massage, or exercise, to relieve pain. 

Progressive muscle relaxation. A cognitive-behavioral strategy in 
which muscles are alternately tensed and then relaxed in a 
systematic fashion. 

Pseudoaddiction. Pattern of drug-seeking behavior of pain patients 
receiving inadequate pain management that can be mistaken for 
addiction. 

Psychological dependence (addiction). Pattern of compulsive drug use 
characterized by a continued craving for an opioid and the need to use 
the opioid for effects other than pain relief. 

Psychosocial intervention. A therapeutic intervention that uses cogni- 
tive, cognitive-behavioral, behavioral, and supportive interventions to 
relieve pain. These include patient education, interventions aimed at 
aiding relaxation, psychotherapy, and structured or peer support. 

Relaxation. A state of relative freedom from both anxiety and skeletal 
muscle tension. 

Self-statement. Involves instructing patients to substitute positive 
thoughts for such negative ones as "I can't stand this" or "How much 
longer will this go on?" 

Suffering. A state of severe distress associated with events that 
threaten the intactness of the person. 

Tolerance. A common physiologic result of chronic opioid use; it 
means that a larger dose of opioid is required to maintain the same 
level of analgesia. 

TENS. A method of producing electroanalgesia through electrodes 
applied to the skin. 



188 



Contributors 

Cancer Pain Panel Members: 
Biosketches 

Ada K. Jacox, RN, PhD, FAAN, Co-Chair 1991-94 

Independence Foundation Chair of Health Policy 

School of Nursing 

The Johns Hopkins University 

Baltimore, Maryland 

Specialties: Health Policy, Outcomes Research 

Dr. Jacox is a nurse who has had extensive experience in health policy 
and in the analysis of scientific evidence for application to clinical 
practice. She has conducted research on pain assessment and has 
published her work in numerous publications. She serves as editor of 
the Mosby Year Book of Pain. Her responsibilities as Co-Chair of the 
panel included overseeing the process of review of scientific evidence 
and, together with the Co-Chairs, directing the work of the panel, 
consultants, and staff, in the development, testing, and dissemination 
of the guidelines. 



Daniel B. Carr, MD, Co-Chair 1991-92 

Special Consultant 1992-94 

Director, Division of Pain Management 

Department of Anesthesia 

Massachusetts General Hospital 

Boston, Massachusetts 

Specialties: Anesthesiology, Endocrinology 

Dr. Carr has extensive clinical and research experience in pain 
management. In addition to cochairing the first half of the panel's 
work, Dr. Carr wrote and edited major sections of the guideline. Dr. 
Carr is Associate Professor of Anesthesiology and Medicine at 
Harvard Medical School. He participated in the development of the 
American Pain Society's quality assurance standards for pain manage- 
ment. Dr. Carr serves on the editorial board of the Clinical Journal of 
Pain and is Editor-in-Chief of Pain: Clinical Update, published by the 
International Association for the Study of Pain. His special interests 
are stress physiology, analgesic peptides, and burn pain. 



189 



Management of Cancer Pain 

Richard Payne, MD, Co-Chair 1992-94 

Panel Member 1991-92 

Director, Pain and Symptom Management Section 

MD Anderson Cancer Center 

Houston, Texas 

Specialties: Neurology, Oncology 

Dr. Payne has done extensive research on opioid analgesic pharmacol- 
ogy in cancer pain and sickle cell pain. He was a member of the Ad 
Hoc Subcommittee on Medical School Courses and Curricula, 
International Association for the Study of Pain. He is a member of the 
Editorial Board of the Clinical J owned of Pain and a member of the 
Board of Directors of the American Pain Society. Dr. Payne's respon- 
sibilities as Co-Chair included writing major sections of the guideline 
and directing the work of the panel. 



Charles B. Berde, MD, PhD 1992-94 

Director, Pain Treatment Service 

Children's Hospital 

Boston, Massachusetts 

Specialties: Pediatrics, Anesthesia, Critical Care 

Dr. Berde is an Associate Professor of Anesthesiology and Pediatrics 
at Harvard Medical School, the Director of the Pain Treatment 
Service at the Children's Hospital, and a nationally recognized author- 
ity on pain management in children. He has extensive clinical and 
research experience in pain management and mechanisms of pain and 
its relief. Dr. Berde is the Scientific Editor of the International 
Association for the Study of Pain Newsletter and is on the Editorial 
Board of the American Pain Society Journal 



190 



Contributors 

William Breitbart, MD 1991-94 

Associate Member 

Memorial Sloan-Kettering Cancer Center 

New York, New York 

Specialties: Psychiatry, Internal Medicine 

Dr. Breitbart is an Assistant Professor of Psychiatry at Cornell 
University Medical College, Medical Director of the Memorial 
Hospital Psychiatry Service Home Care Program, and a nationally 
recognized authority on psychiatric aspects of cancer pain manage- 
ment. He has written about psychiatric and psychological contribu- 
tions to symptom management in cancer and AIDS patients. Dr. 
Breitbart is Co-Chair of the International Association for the Study of 
Pain's Task Force on Pain in AIDS. He is a founding member of the 
American Society for Psychiatric Oncology/ AIDS and is on the 
Editorial Board of the Journal of Pain and Symptom Management. 



Joanna M. Cain, MD 1992-94 

Director, Women's Clinic 

Division of Gynecologic Oncology 

University of Washington Hospital 

Seattle, Washington 

Specialties: Obstetrics, Gynecologic Oncology 

Dr. Cain is a gynecologic oncologist with extensive clinical experience 
in the management of pain in patients with pelvic malignancy. She is an 
Associate Professor of Obstetrics and Gynecology at the University of 
Washington Medical School. She has an interest and expertise in 
medical ethics and is a member of the Association of Professors of 
Gynecology and Obstetrics Ethics Committee. She also serves as a 
consultant on ethical issues to the National Institutes of Health. 



191 



Management of Cancer Pain 

C. Richard Chapman, PhD 1991-92 

Professor, Department of Anesthesiology 
University of Washington School of Medicine 
Director, Pain and Toxicity Research Program 
Fred Hutchinson Cancer Research Center 
Seattle, Washington 
Specialty: Psychology 

Dr. Chapman is a psychologist who has studied pain since the early 
1970's. His research on both experimental and clinical pain has 
focused on the assessment and treatment of acute and chronic pain, 
including cancer pain and acupuncture. He brought to the panel an 
understanding of psychological interventions for pain and opioid anal- 
gesia. He is a past member of the Board of Directors of the American 
Pain Society and Editor of the Bulletin of the American Pain Society. 



Charles S. Cleeland, PhD 1992-94 

Director, Pain Research Group 

Professor of Neurology 

University of Wisconsin Medical School 

Madison, Wisconsin 

Specialty: Psychology 

Dr. Cleeland is well known for his work documenting the severity and 
effect of pain due to cancer as well as the variability in cancer pain 
treatment. Dr. Cleeland is Chair of the United States Cancer Pain 
Relief Committee and has served as Co-Chair of the National Cancer 
Institute's Cancer Pain Work Group. He is the Director of the World 
Health Organization's Collaborating Center for Symptom Evaluation 
for the cancer unit and has participated in the development of WHO 
international demonstration projects in cancer pain relief. 



Betty R. Ferrell, RN, PhD, FAAN 1991-94 

Associate Research Scientist, Nursing Research 
City of Hope Medical Center 
Duarte, California 
Specialties: Oncology, Nursing 

Dr. Ferrell has expertise as a researcher and clinician in the manage- 
ment of cancer pain, particularly pain in the elderly patient and pain 
at home. She has had experience in incorporating pain management 
into quality assurance programs. Dr. Ferrell's other research interests 
are in ethical and clinical decisionmaking in cancer pain, quality of life 
in cancer survivors, and the cost of pain management. 



192 



Contributors 

Rebecca S. Finley, PharmD, MS 1992-94 

Head, Section of Pharmacy Services 
University of Maryland Cancer Center 
Associate Professor of Oncology 
Associate Professor of Pharmacy Practice 
University of Maryland School of Pharmacy 
Baltimore, Maryland 
Specialty: Institutional Pharmacy 

Dr. Finley has expertise as a researcher, clinician, and educator in the 
management of chemotherapy and pain in cancer patients. She 
currently serves on the Board of Directors of the American Society of 
Hospital Pharmacists (ASHP) and is a former Chairperson for the 
ASHP Special Interest Group on Oncology. She currently chairs the 
Editorial Advisory Board, Panel on Oncology for the journal Annals 
of Pharmacotherapy. 



Nancy O. Hester, RN, PhD, FAAN 1991-94 

Associate Professor, School of Nursing 
University of Colorado Health Sciences Center 
Denver, Colorado 
Specialties: Pediatrics, Research Methods 

Dr. Hester, a nurse, began studying pain in children in 1975. Her 
research focuses on the child's perception of pain experiences; comfort 
for the child in pain; the measurement of procedural, postoperative, 
and cancer pain in children; nurse clinical decisionmaking about pain 
in children; and pain assessment and management practices on pedi- 
atric units. She was a member of the National Center for Nursing 
Research's panel to set priorities in the study of pain and currently 
serves on the Nursing Research Study Section for the National 
Institutes of Health. 



193 



Management of Cancer Pain 

C. Stratton Hill, Jr., MD 1991-92 

Professor of Medicine 

University of Texas 

MD Anderson Cancer Center 

Houston, Texas 

Specialty: Oncology 

Dr. Hill was the Director of MD Anderson's Pain Service for 10 years. 
His major interest is cultural and societal barriers to adequate pain 
control when opioids are required. He coauthored a bill, The 
Intractable Pain Treatment Act, and was instrumental in its passage 
by the 71st Session of the Texas Legislature in July 1989. Dr. Hill is on 
the Editorial Board of the Pain Clinic Journal. 



W. David Leak, MD, FACPM 1992-94 

Medical Director, Pain Control Consultants 
Westerville, Ohio 
Specialty: Pain Medicine 

Dr. Leak is an adjutant staff member at the Cleveland Clinic 
Foundation. His major interests are in the neuroaugmentation of the 
CNS and the cultural and social aspects of pain management. He 
serves on the Examination Committee of the American College of 
Pain Medicine. Dr. Leak is Chairman of the National Medical 
Association Political Action Committee. 



Arthur G. Lipman, PharmD 1991-92 

Professor of Clinical Pharmacy 

College of Pharmacy 

University of Utah 

Salt Lake City, Utah 

Specialty: Pharmacology in Pain Symptom Control 

Dr. Lipman practices in the Pain Management Center at University 
Hospital, University of Utah. He was a member of the National Cancer 
Institute Demonstration Project of Hospice Care in New Haven, 
Connecticut, and is now pharmacologic consultant and a past president 
of Community Hospice in Utah. His research interests focus on cancer 
pain management. While on sabbatical leave from the University of 
Utah, he collaborated in the development of a cancer pain data system 
at Sir Michael Sobell House, Churchill Hospital, University of Oxford, 
England. Dr. Lipman serves on the Pain Management Advisory Group 
of the American Cancer Society and is Editor of the Journal of 
Pharmaceutical Care in Pain and Symptom Control 



194 



Contributors 

Catherine L. Logan 1992-94 

Executive Director and Founder, Living Through Cancer, Inc. 
Board of Advisors, National Coalition for Cancer Survivorship 
Albuquerque, New Mexico 
Consumer Representative 

Catherine Logan is a 15-year survivor of invasive cervical cancer and 
the cofounder of the National Coalition for Cancer Survivorship. She 
served as the first Executive Director of this organization from 1986 to 
1991. She is an outspoken advocate for community-based, grassroots 
cancer support organizations and has given presentations on the sur- 
vivorship movement at conferences and workshops across the country. 



Charles L. McGarvey, PT, MS 1991-92 

Chief, Physical Therapy Section 
Rehabilitation Medicine Department 
Warren G. Magnuson Clinical Center 
National Institutes of Health 
Bethesda, Maryland 
Specialty: Physical Therapy 

Mr. McGarvey is a physical therapist and a Commander in the 
Commissioned Corps of the U.S. Public Health Service. Before 
coming to the National Institutes of Health in 1983, he was Deputy 
Chief of the Physical Therapy Department at the U.S. Public Health 
Service Hospital in Whiteriver, Arizona, and before that a staff physi 
cal therapist at the U.S. Public Health Service Hospital in Norfolk, 
Virginia. He is past President of the Oncology Section of the 
American Physical Therapy Association and Editor of the text 
Physical Therapy for the Cancer Patient. 



Christine A. Miaskowski, RN, PhD, FAAN 1991-92 

Associate Professor 
Department of Physiological Nursing 
University of California, San Francisco 
San Francisco, California 
Specialty: Oncology 

Dr. Miaskowski is an oncology clinical nurse specialist with extensive 
experience in the development of standards of practice and their 
monitoring for quality assurance. She served as a member of the 
American Pain Society committee that developed quality assurance 
standards for pain management. Her research focuses on mechanisms 
of opioid-induced analgesia. Dr. Miaskowski is on the Board of 
Directors of the American Pain Society. 

195 



Management of Cancer Pain 

David Stevenson Mulder, MD 1991-92 

Professor of Surgery, McGill University 
Surgeon-in-Chief, Montreal General Hospital 
Montreal, Quebec, Canada 
Specialty: Cardiothoracic Surgery 

Dr. Mulder is an academic surgeon with a specialty in cardiothoracic 
surgery. He has authored, among numerous publications, texts on 
surgical research and acute life support. In 1989, he was Secretary of 
the International Trauma Society and, in 1990, President of the 
Canadian Association of Clinical Surgeons. 



Judith A. Paice, RN, PhD 1992-94 

Clinical Specialist, Pain Management 
Neuroscience Institute 

Rush-Presbyterian-St. Luke's Medical Center 
Chicago, Illinois 
Specialties: Neurosurgery, Oncology 

Dr. Paice is a nurse who has written and lectured extensively in the 
area of cancer pain management, including the use of intrathecal 
morphine infusions for intractable cancer pain. Her research interests 
are in the physiology of pain transmission and the role of new agents 
in the treatment of neuropathic pain. She has served on the Editorial 
Review Board of Oncology Nursing Forum and currently serves on 
the Board of the Year Book of Oncology Nursing. 



Barbara S. Shapiro, MD 1991-92 

Associate Director, Pain Management Program 

Children's Hospital of Philadelphia 

Assistant Professor of Pediatrics 

University of Pennsylvania School of Medicine 

Philadelphia, Pennsylvania 

Specialties: General Pediatrics, Pain Management 

Dr. Shapiro is a general pediatrician with specialty training in pedi- 
atric hematology and oncology. She participated in the formation of 
an interdisciplinary pediatric pain service, and the majority of her clin- 
ical and research efforts are in the area of pain assessment and 
management. She has been particularly active in the areas of sickle 
cell- and cancer-related pain. 






196 



Contributors 

Edward B. Silberstein, MD, FACNP 1992-94 

Associate Director, E. L. Saenger Radioisotope Laboratory 
University of Cincinnati Medical Center 
Professor of Medicine and Radiology 
University of Cincinnati College of Medicine 
Cincinnati, Ohio 

Specialties: Nuclear Medicine, Internal Medicine, 
Hematology, Oncology 

Dr. Silberstein is a nuclear medicine physician with extensive experi- 
ence in the use of radiopharmaceuticals to palliate metastatic cancer 
pain. He is a prolific researcher and has published extensively on the 
use of radiopharmaceuticals. Dr. Silberstein serves as Consultant for 
the United States Pharmacopeia, the Department of Health and 
Human Services, the Centers for Disease Control, the Nuclear 
Regulatory Commission, and the Department of Energy. He is the 
Nuclear Medicine Section Editor of the Journal of the American 
Medical Association. 



Rev. Robert S. Smith, PhD 1991-92 

Director, Institute for Medicine in Contemporary Society 
State University Medical Center at Stony Brook 
Stony Brook, New York 
Specialties: Religion, Ethics 

Father Smith was ordained to the Roman Catholic priesthood in 1958. 
During the past 10 years, he has taught bioethics in the School of 
Medicine, State University of New York, Stony Brook, and has served 
on numerous state and national boards dealing with medicine and 
ethics. He is a member of the New York State Governor's Task Force 
on Life and Law and the New York State Cardiac Advisory 
Committee; Fr. Smith is on the Board of Directors of the United 
Network for Organ Sharing. 

Jeanne Stover 1991-92 

Cofounder of Living Through Cancer, Inc. 
Sandia Park, New Mexico 
Consumer Representative 

Ms. Stover was a 23-year survivor of metastatic breast cancer who had 
experienced cancer pain for many years. She represented the National 
Coalition for Cancer Survivorship on the panel. Ms. Stover was 
cofounder of the Living Through Cancer Survivorship Center, one of 
the country's largest and most active community-based local cancer 
support/survivorship organizations. She died in January 1993. 

197 



Management of Cancer Pain 

Carole V. Tsou, MD 1991-92 

Residency Program Director 
University of Hawaii 
Department of Family Practice 
Mililani, Hawaii 
Specialty: Family Medicine 

Dr. Tsou is a family physician who has been involved in the education 
of family physicians at the undergraduate, graduate, and continuing 
education levels. She completed a research fellowship in family medi- 
cine at the University of California, Los Angeles, and formerly was 
Assistant Director of the Education Division of the American 
Academy of Family Physicians. 



Loretta Vecchiarelli 1991-92 

Ludlow, Massachusetts 
Consumer Representative 

Ms. Vecchiarelli is a rehabilitation counselor and a physician's assis- 
tant. She suffered serious burn injuries as an adult and subsequently 
underwent treatment and rehabilitation, which included experiencing 
repeated episodes of treatment-induced pain. She has served as a 
consumer representative on the panel. 



David E. Weissman, MD 1992-94 

Associate Professor of Medicine 
Division of Cancer and Blood Diseases 
Medical College of Wisconsin 
Milwaukee, Wisconsin 
Specialties: Internal Medicine, Oncology 

Dr. Weissman has expertise as a clinician, researcher, and educator in 
cancer pain management. He is the Director of the Cancer Pain Role 
Model Program — a physician education program — of the Wisconsin 
Cancer Pain Initiative. He is nationally known for his contributions to 
cancer pain education and his interest in regulatory barriers to cancer 
pain relief. 



198 



Other Contributors 1 



Consultants 

Gerard Anderson, PhD 
Associate Professor of 
Health Policy and Management 
Johns Hopkins University 
Baltimore, Maryland 

Ehud Arbit, MD 

Chief, Neurosurgery Service 

Memorial Sloan-Kettering 

Cancer Center 

New York, New York 

Catherine Berkey, DSc, MA 
Technology Assessment Group 
Harvard University School of 
Public Health 
Boston, Massachusetts 

Andrew P. Brown, MRCP, FRCR 
Radiation Oncologist 
Elliot Hospital 
Manchester, New Hampshire 

Thomas C. Chalmers, MD 
Technology Assessment Group 
Harvard University School of 
Public Health 
Boston, Massachusetts 

June L. Dahl, PhD 
Professor of Pharmacology 
University of Wisconsin-Madison 
Medical School 
Madison, Wisconsin 

Stuart L. Du Pen, MD 

Director, 

Pain Management Service 

Swedish Tumor Institute 

Swedish Medical Center 

Seattle, Washington 



Hurdis Griffith, RN, PhD, FAAN 
Senior Policy Advisor 
Office of Disease Prevention 
and Health Promotion 
U.S. Public Health Service, 
Department of Health and 
Human Services 
Washington, District of Columbia 

Stuart A. Grossman, MD 
Director, Neuro-Oncology 
Associate Professor of Oncology, 
Medicine, and Neurosurgery 
The Johns Hopkins 
Oncology Center 
Baltimore, Maryland 

Bernard Hammes, PhD 
Gundersen Clinic 
LaCrosse, Wisconsin 

Nora A. Janjan, MD 

Associate Professor of Radiation 

Oncology 

MD Anderson Cancer Center 

Houston, Texas 

David E. Joranson, MSSW 
Associate Director 
Pain Research Group 
University of Wisconsin-Madison 
Medical School 
Madison, Wisconsin 

E. M. Kolassa, MBA 
Research Associate 
Research Institute of 
Pharmaceutical Sciences 
The University of Mississippi 
University, Mississippi 



] Being listed in this section does not necessarily imply endorsement of the guideline. 

199 



Management of Cancer Pain 

Mathew Lefkowitz, MD 

Assistant Professor of 

Anesthesiology 

Director, 

Pain Management Service 

State University of New York 

Health Science Center at 

Brooklyn 

Brooklyn, New York 

Margo McCaffery, RN, 

MS, FAAN 

Consultant in the Nursing Care 

of Patients with Pain 

Los Angeles, California 

Patricia A. McGrath, PhD 
Director, Child Health 
Research Institute 
University of Western Ontario 
at the Children's Hospital of 
Western Ontario 
London, Ontario, Canada 

Frederick Mosteller, PhD 

Professor 

Department of Health Policy 

and Management 

Harvard University School 

of Public Health 

Boston, Massachusetts 

Raphael E. Pollock, MD, PhD 
Associate Professor of Surgery 
Deputy Chairman, Department 
of Surgical Oncology 
University of Texas 
MD Anderson Cancer Center 
Houston, Texas 






Robyn Shapiro, JD 
Director, Center for the 
Study of Bioethics 
Medical College of Wisconsin 
Milwaukee, Wisconsin 

Vivian R. Sheidler, RN, MS 
Clinical Nurse Specialist 
Johns Hopkins Oncology Center 
Baltimore, Maryland 

Judith A. Spross, MS, RN, 
OCN, FAAN 

Oncology Nurse Consultant 
Boston, Massachusetts 

Sridhar V. Vasudevan, MD 
Clinical Professor of Physical 
Medicine and Rehabilitation 
Medical Director 
Pain Rehabilitation Center 
Elmbrook Memorial Hospital 
Brookfield, Wisconsin 

Anna Williams, RN, MN 
Clinical Nurse Specialist 
Swedish Tumor Institute 
Swedish Medical Center 
Seattle, Washington 

Melissa Wolff, MS, PT 

Coordinator 

Pain Consultants Network 

University of Tennessee 

Medical Center 

Knoxville, Tennessee 






200 



Peer Reviewers 



Barbara R. Abela, RNC 
Nursing Supervisor 
Visiting Nurse Association of 
Southeast Michigan 
Detroit, Michigan 

Robert G. Addison, MD 

Director of Medical Planning 

Professor, 

Clinical Orthopaedic Surgery 

Professor, 

Clinical Rehabilitation Medicine 

Rehabilitation Institute 

of Chicago 

Chicago, Illinois 

Barbara Lewin Allen, MSN 
Nursing Supervisor 
Visiting Nurse Association 
of Southeast Michigan 
Oak Park, Michigan 

John Ambre, MD, PhD 
Director, Toxicology and 
Drug Abuse 

American Medical Association 
Chicago, Illinois 

Paul N. Anderson, MD 
Founder, Director 
Cancer Center of 
Colorado Springs 
Colorado Springs, Colorado 

Gerald M. Aronoff, MD 
Director, Boston Pain Center 
Assistant Clinical Professor 
Tufts Medical School 
Melrose, Massachusetts 



Michael A. Ashburn, MD 
Director, Acute Pain Service 
Assistant Professor of 
Anesthesiology 
University of Utah 
Health Science Center 
Salt Lake City, Utah 

James Atkins, MD 

Oncologist 

North Carolina Pain Initiative 

Goldsboro, North Carolina 

Carol B aimer, PharmD 
Associate Professor 
University of Colorado 
School of Pharmacy 
Denver, Colorado 

Anne E. Belcher, PhD 
Associate Professor and Chair 
University of Maryland, 
School of Nursing 
Baltimore, Maryland 

Miles J. Belgrade, MD 
Director, Hennepin Pain Clinic 
Department of Neurology 
Hennepin County 
Medical Center 
Minneapolis, Minnesota 

Elizabeth Benson, RN 
Hospice Nursing Coordinator 
Lutheran Hospice Care 
Wheat Ridge, Colorado 

J. Andrew Billings, MD 
Assistant Clinical Professor 
of Medicine 

Harvard Medical School 
Associate Physician 
Massachusetts General Hospital 
Boston, Massachusetts 



201 



Management of Cancer Pain 

Diane Blum, MSW 
Executive Director 
Cancer Care, Inc. 
New York, New York 

Albert L. Blumberg, MD 
Vice-Chairman 
Department of 
Radiation Oncology 
Greater Baltimore 
Medical Center 
Baltimore, Maryland 

Nancy L. Bohnet, RN, 
MN, FAAN 
President/CEO 
Home Health Services 
Foundation, Inc. 
Butler, Pennsylvania 

John D. Bonnet, MD 
Scott & White Clinic 
Temple, Texas 

Philip O. Bridenbaugh, MD 
Professor and Chairman 
Department of Anesthesiology 
University of Cincinnati 
Medical Center 
Cincinnati, Ohio 

Dorothy Y. Brockopp, RN, PhD 
Nurse Researcher 
Associate Professor of Nursing 
University of Kentucky 
Lexington, Kentucky 

Marion E. Broome, RN, PhD 
Professor and Assistant 
Chairperson 
Maternal-Child Nursing 
Rush-Presbyterian-St. Luke's 
Medical Center 
Chicago, Illinois 



Beverly A. Buck, RT 
Education and Development 
Coordinator 
Joint Center for 
Radiation Therapy 
Harvard Medical School 
Boston, Massachusetts 

James N. Campbell, MD 
Associate Director 
Department of Neurosurgery 
Professor of Neurosurgery 
Johns Hopkins University 
Medical School 
Baltimore, Maryland 

Hugh Chaplin, Jr., MD 
Emeritus Professor of 
Medicine and Pathology 
Hospice Volunteer 
Washington University 
Medical Center 
St. Louis, Missouri 

Peggy Christ, RN, ET, CIC 
Nurse Epidemiologist/ 
Enterostomal Therapist 
Jennie Edmundson Hospital 
Council Bluffs, Iowa 

David E. Cohen, MD 

Director, 

Pain Management Program 

Children's Hospital 

of Philadelphia 

Philadelphia, Pennsylvania 

Kathleen Colburn, MA 
Executive Director 
Hospice of Central Iowa 
Des Moines, Iowa 

B. Eliot Cole, MD 
Medical Director, Senior Care 
Harris Hospital 
Newport, Arkansas 






202 



Contributors 



Joseph C. Conger, RPH 
Pharmacist 
Consultant Pharmacy 
Flint, Michigan 

Laurel Archer Copp, PhD, DHL 

Professor 

University of North Carolina 

Chapel Hill, North Carolina 

Charles J. Cote, MD 
Associate Professor 
of Anaesthesia 
Harvard Medical School 
Massachusetts General Hospital 
Boston, Massachusetts 

Nessa Coyle, RN, MS 

Director, 

Supportive Care Program 

Department of Neurology 

Pain Service 

Memorial Sloan-Kettering 

Cancer Center 

New York, New York 

Patrick J. Coyne, RN, CS, MSN 
Nursing Pain Control Consultant 
Medical College of 
Virginia Hospitals 
Richmond, Virginia 

Carol P. Curtiss, RN, MSN, OCN 
Oncology Manager/Consultant 
Franklin Medical Center 
Greenfield, Massachusetts 

Lynn Czarniecki, RN, MSN 
Children's Hospital 
AIDS Program 
Newark, New Jersey 

June L. Dahl, PhD 
Professor of Pharmacology 
University of Wisconsin-Madison 
Medical School 
Madison, Wisconsin 



JoAnn Dalton, RN, EdD 
Associate Professor 
University of North Carolina 
at Chapel Hill 
School of Nursing 
Chapel Hill, North Carolina 

Ann L. Daum, RN, MS, CS 
Psychiatric Liaison Nurse 
Clinical Specialist 
Departments of Nursing 
and Psychiatry 
Rhode Island Hospital 
Providence, Rhode Island 

Judy M. Diekmann, RN, 
DEd, OCN 
Associate Professor 
Chair, Health Restoration 
University of 
Wisconsin-Milwaukee 
School of Nursing 
Milwaukee, Wisconsin 

William R. Dinwoodie, MD 
Associate Professor of Medicine 
H. Lee Moffitt Cancer Center 
University of South Florida 
Tampa, Florida 

Marion B. Dolan, RN 

President 

Heritage Home Health 

Merideth, New Hampshire 

Marilee Donovan, RN, PhD 
Associate Hospital Director 
Oregon Health Sciences University 
Portland, Oregon 

Mary Jo Dropkin, RN, MSN 
Clinical Nurse Specialist 
Head and Neck Service 
Memorial Sloan-Kettering 
Cancer Center 
New York, New York 



203 



Management of Cancer Pain 



Jeffrey J. Eckardt, MD 
Professor of Surgery 
and Orthopaedics 
University of California, 
Los Angeles 

Center for Health Sciences 
Los Angeles, California 

W. Thomas Edwards, PhD, MD 

Associate Professor of 

Anesthesiology 

Director, Pain Relief Service 

University of Washington 

Harborview Medical Center 

Seattle, Washington 

Joann M. Eland, RN, PhD, 

NAP, FAAN 

Associate Professor of Nursing 

University of Iowa 

Iowa City, Iowa 

Thomas E. Elliott, MD 
Director of Education and 
Research 
Duluth Clinic 
Duluth, Minnesota 

Neil M. Ellison, MD 
Associate, Medical Oncology 
Geisinger Medical Center 
Danville, Pennsylvania 

Joyce M. Engel, PhD, OTR 
Assistant Professor of 
Occupational Therapy 
University of Wisconsin-Madison 
Madison, Wisconsin 

Serdar Erdine 
Professor, Chairman 
Department of Algology 
Medical Faculty of 
Istanbul University 
Istanbul, Turkey 



James Erickson III, MD 
Professor of Clinical Anesthesia 
Northwestern University 
Chicago, Illinois 

Margaret Faut-Callahan 
DNSc, CRNA, FAAN 
Professor 
Rush University 
College of Nursing 
Chicago, Illinois 

Fawzy I. Fawzy, MD 
Professor, Deputy Chairman 
University of California, 
Los Angeles 
School of Medicine 
Los Angeles, California 

Phoebe A. Fernald, RN, 
MS, OCN 
Clinical Nurse 
Specialist-Oncology 
Rhode Island Hospital 
Providence, Rhode Island 

F. Michael Ferrante, MD 
Director, Pain Treatment Center 
Department of Anesthesia 
Brigham and Women's Hospital 
Boston, Massachusetts 

Walter B. Forman, MD, FACP 
Associate Chief of Staff 
Geriatrics/Extended Care Service 
Associate Professor 
Medicine, Geriatrics 
VA Medical Center 
Albuquerque, New Mexico 

Michael E. Frederich, MD 
Medical Director 
Hospice of Southern Illinois, Inc. 
Belleville, Illinois 



204 



Contributors 



Marvin Frederickson, MD 
Medical Oncology Section 
Medical Director of Group 
Health Hospice Program 
Group Health Cooperative of 
Puget Sound 
Seattle, Washington 

Robert W. Frelick, MD, FACP 
Consultant, Chronic Disease 
Control and Prevention 
Delaware Division of 
Public Health 
Wilmington, Delaware 

Rollin M. Gallagher, MD 

Director, The Pain Center 

Associate Professor, 

Psychiatry 

State University of New York at 

Stony Brook 

Stony Brook, New York 

Richard Gannon, PharmD 
Director of Pharmacy 
Pain Control 
Hartford Hospital 
Hartford, Connecticut 

Fannie Gaston- Johansson, 

DMSc, RN, FAAN 

Director of Post-Masters Program 

Associate Professor 

Elsie M. Lawler Chair 

Johns Hopkins University 

Baltimore, Maryland 

Madeline E. Gerken, MD 

Staff Oncologist 

VA Medical Center 

Medical Director 

Home Health and Hospice Care 

Nashua, New Hampshire 

Myra Glajchen, DSW 
Assistant Director 
Cancer Care, Inc. 
New York, New York 



Gilbert R. Gonzales, MD 
Senior Associate Consultant 
Mayo Clinic Scottsdale 
Scottsdale, Arizona 

Lee Green, MD, MPH 
Assistant Professor 
Department of Family Practice 
University of Michigan 
Ann Arbor, Michigan 

Donna B. Greenberg, MD 
Associate Psychiatrist 
Assistant Professor Psychiatry 
Massachusetts General 
Hospital/Harvard Medical School 
Boston, Massachusetts 

Wendy Gilbert Gronbeck, 

RN, OCN, MA 

Nurse Clinician 

University of Iowa Hospitals 

and Clinics 

Iowa City, Iowa 

Stuart A. Grossman, MD 
Director, Neuro-Oncology 
Associate Professor of Oncology, 
Medicine, and Neurosurgery 
The Johns Hopkins 
Oncology Center 
Baltimore, Maryland 

Stephen A. Gudas, PT, PhD 
Assistant Professor 
Departments of Rehabilitation, 
Medicine, and Anatomy 
Medical College of Virginia 
Richmond, Virginia 

Stephen Pernice Gullo, PhD 
Director, Health Policies 
and Planning 

American Institute for Life 
Threatening Illness and Loss 
Columbia-Presbyterian 
Medical Center 
New York, New York 



205 



Management of Cancer Pain 



Susan Jane Hagan, BSN, 

MS, ARNP 

Coordinator — Pain Programs 

James A. Haley 

Veterans Hospital 

Tampa, Florida 

Gerald E. Hanks, MD 

Chairman 

Department of Radiation Therapy 

Professor of Radiation Therapy 

Fox Chase Cancer Center 

Philadelphia, Pennsylvania 

Kenneth M. Hargreaves, 
DDS, PhD 

Associate Professor of 
Endodontics and Pharmacology 
University of Minnesota 
School of Dentistry 
Minneapolis, Minnesota 

Edward P. Hargus, MD 
Director of 

Pain Management Services 
Lawrence and Memorial Hospital 
New London, Connecticut 

William N. Harsha, MD, MS, JD 
President and Board of Advisors 
American Academy of 
Pain Management 
Oklahoma Spine/Pain Clinic 
Oklahoma City, Oklahoma 

Samuel J. Hassenbusch, MD, PhD 

Associate Professor 

Neurosurgery 

MD Anderson Cancer Center 

Houston, Texas 

Laura J. Hilderley, RN, MS 
Clinical Nurse Specialist 
Radiation Oncology 
Warwick, Rhode Island 



Reginald Ho, MD 

Chief, Department of Oncology 

and Hematology 

Straub Clinic and Hospital 

Honolulu, Hawaii 

Marilyn Hockenberry-Eaton, 
PhD, RN-CS, PNP 
Associate Professor 
Emory University 
Atlanta, Georgia 

Jimmie Holland, MD 
Chief, Psychiatry Service 
Memorial Sloan-Kettering 
Cancer Center 
New York, New York 

Victor J. Hruby, PhD 
Regents Professor 
Department of Chemistry 
University of Arizona 
Tucson, Arizona 

Jean M. Huls, RN, BSN 
Director of Nursing 
Hospice of the Valley 
Phoenix, Arizona 

Terri L. Imada, RN, MS 
Oncology Clinical Nurse Specialist 
Kuakini Medical Center 
Honolulu, Hawaii 

Nora A. Janjan, MD 
Associate Professor of 
Radiation Oncology 
MD Anderson Cancer Center 
Houston, Texas 

David E. Joranson, MSSW 
Associate Director 
Pain Research Group 
University of Wisconsin-Madison 
Medical School 
Madison, Wisconsin 



206 



Contributors 



C. Celeste Johnston, RN, DEd 
Associate Professor 
McGill University 
Montreal, Quebec, Canada 

Maryalice Jordan-Marsh, RN, PhD 
Director of Nursing 
Research Division 
Harbor-University of California, 
Los Angeles, Medical Center 
Torrance, California 

A. Robert Kagan, MD 
Chief, Radiation Oncology 
Southern California Kaiser 
Permanente Medical Group 
Los Angeles, California 

Wayne Katon, MD 
Professor of Psychiatry 
Department of Psychiatry and 
Behavioral Sciences 
University of Washington 
Medical School 
Seattle, Washington 

Pamela L. Kedziera, RN, 
MSN, OCN 
Clinical Manager — 
Pain Management Center 
Fox Chase Cancer Center 
Philadelphia, Pennsylvania 

John F. Kerege, PharmD 
Clinical Specialist-Oncology 
Oregon Health Sciences University 
Portland, Oregon 

Steven A. King, MD, MS 
Associate Director, Pain Center 
Associate Professor 
Department of Psychiatry and 
Human Behavior 
Jefferson Medical College 
Jefferson Pain Center 
Philadelphia, Pennsylvania 



Barry M. Kinzbrunner, MD, FACP 
Vice President, Clinical Services 
Vitas Healthcare Corporation 
Miami, Florida 

Linda U. Krebs, RN, MS, OCN 
Nursing Oncology 
Program Leader 
University of Colorado 
Cancer Center 
Denver, Colorado 

Stacie E. Krick, PharmD 
Assistant Professor of 
Pharmacy Practice 
Campbell University 
School of Pharmacy 
Buies Creek, North Carolina 

Austin H. Kutscher, DDS 
Professor of Dentistry 
(in Psychiatry) 
College of Physicians 
and Surgeons 
Columbia University 
New York, New York 

Robert R. Kutzner, MD 

Director 

Indiana Pain Institute 

Bedford, Indiana 

Jacqueline A. LaPerriere, RPh 
Pain Service Coordinator 
H. Lee Moffitt Cancer Center 
Tampa, Florida 

Allen Lebovits, PhD 
Clinical Associate Professor 
Department of Anesthesiology 
State University of New York 
Health Science Center 
at Brooklyn 
Brooklyn, New York 



207 



Management of Cancer Pain 



Mathew H. M. Lee, MD, 
MPH, FACP 

Professor and Acting Chairman 

Department of Rehabilitation 

Medicine 

New York University 

Medical Center 

New York, New York 

Mathew Lefkowitz, MD 

Assistant Professor of 

Anesthesiology 

Director, 

Pain Management Service 

State University of New York 

Health Science Center 

at Brooklyn 

Brooklyn, New York 

Mark J. Lema, MD, PhD 

Chairman, Department of 

Anesthesiology 

Roswell Park Cancer Institute 

Buffalo, New York 

Michael H. Levy, MD, PhD 

Co-Director, 

Pain Management Center 

Fox Chase Cancer Center 

Philadelphia, Pennsylvania 

Leonard Lichtblau, PhD 
Assistant Professor 
Department of Pharmacology 
University of Minnesota 
Minneapolis, Minnesota 

Keith D. Lillemoe, MD 
Associate Professor of Surgery 
Johns Hopkins University 
School of Medicine 
Baltimore, Maryland 



Philipp M. Lippe, MD, FACS, 

FACPM 

Clinical Associate Professor of 

Neurosurgery 

Stanford University 

San Jose, California 

The Rev. Jerry L. Loch, 
CRNA, PhD 

Pain Management Service 
Kishwaukee Hospital 
DeKalb, Illinois 

John D. Loeser, MD 
Professor, Neurological Surgery 
and Anesthesiology 
University of Washington 
Pain Center 
Seattle, Washington 

David R. Longmire, MD, ABEN 

Adjunct Staff, Pain Management 

Center 

Department of General 

Anesthesiology 

Division of Research 

Anesthesiology 

Cleveland Clinic Foundation 

Cleveland, Ohio 

Neil MacDonald, MD, FRCP(C) 
Professor, Palliative Medicine 
University of Alberta 
Edmonton, Alberta, Canada 

Janice Mathews, RN, MEd, MA 
Pain Management Specialist 
Heritage Home Health 
Meredith, New Hampshire 

Mitchell B. Max, MD 
Chief, Clinical Trials Unit 
Neurobiology and 
Anesthesiology Branch 
National Institute of 
Dental Research 
National Institutes of Health 
Bethesda, Maryland 



208 



Contributors 



Margo McCaffery, RN, 

MS, FAAN 

Consultant in the Nursing Care 

of Patients with Pain 

Los Angeles, California 

Ruth McCorkle, RN, PhD, 

FAAN 
Professor 
School of Nursing 
University of Pennsylvania 
Philadelphia, Pennsylvania 

Francis J. McDonnell, MD, 

FFARCSI 

Assistant Professor of 

Anesthesiology 

University of Kentucky 

Lexington, Kentucky 

Patrick J. McGrath, PhD 

Professor 

Department of Psychology 

Dalhousie University 

Halifax, Nova Scotia, Canada 

Deborah B. McGuire, RN, 
PhD, FAAN 

Edith F. Honeycutt Chair 
in Oncology Nursing 
Associate Professor of Nursing 
Nell Hodgson Woodruff 
School of Nursing 
Emory University 
Atlanta, Georgia 

Susan C McMillan, PhD, RN 
American Cancer Society 
Professor of Oncology Nursing 
University of South Florida 
College of Nursing 
Tampa, Florida 

Faye McNaull, RN, CS, 

MPH, MBA 

Nursing Director 

Kansas University Cancer Center 

Kansas City, Kansas 



Ronald Melzack, PhD 
E. P Taylor Professor 
Department of Psychology 
McGill University 
Montreal, Quebec, Canada 

Susan Michlovitz, MS, PT 
Adjunct Associate Professor 
Hahnemann University 
Programs in Physical Therapy 
Philadelphia, Pennsylvania 

Bonnie L. Minter, RN, MS 
Pediatric Hospice Nurse 
Massachusetts Cancer 
Pain Initiative 
Boston, Massachusetts 

Jean B. Moen, RN, MS 
Senior Vice-President, 
Operations 

American Cancer Society 
Georgia Division 
Atlanta, Georgia 

Michael F. Mulroy, MD 
Staff Anesthesiologist 
Department of Anesthesiology 
Virginia Mason Medical Center 
Seattle, Washington 

Maryann R. Nalley, BS, RN 

Director of Professional 

Education 

American Cancer Society 

Missouri Division 

Jefferson City, Missouri 

John Neville, MD 
Medical Director 
Vesper Society Hospice 
San Leandro, California 

Lorenz K. Y. Ng, MD 
Director, Chronic Pain Program 
National Rehabilitation Hospital 
Washington, District of Columbia 



209 



Management of Cancer Pain 



Doris G. Nuttelman, RN, EdD 

Executive Director 

New Hampshire Board 

of Nursing 

Concord, New Hampshire 

Donna O'Shaughnessy, RN, OCN 

Director 

Saint James Hospice 

Pontiac, Illinois 

James M. Oleske, MD, MPH 
Francois-Xavier Bagnoud 
Professor of Pediatrics 
New Jersey Medical School 
Newark, New Jersey 

Paul M. Paris, MD, FACEP 
Associate Professor and Chief 
Division of Emergency Medicine 
University of Pittsburgh 
School of Medicine 
Pittsburgh, Pennsylvania 

Steven D. Passik, PhD 
Clinical Assistant 
Attending Psychologist 
Memorial Sloan-Kettering 
Cancer Center 
New York, New York 

Richard B. Patt, MD 
Associate Professor 
Anesthesiology, Psychiatry, 
and Oncology 
University of Rochester 
School of Medicine and Dentistry 
Rochester, New York 

David C. Pederson, CRNA 
C. R. Nurse Anesthetist 
American Association of 
Nurse Anesthetists 
Carroll, Iowa 



Linda K. Person, BSN 
Nursing Supervisor, Oncology 
Kaiser Foundation Hospital 
Honolulu, Hawaii 

Jack Pinsky, MD 
Associate Clinical Professor 
Director, Pain Medicine 
University of California, Irvine, 
College of Medicine 
Orange, California 

Russell K. Portenoy, MD 

Director of Analgesic Studies, 

Pain Service 

Memorial Sloan-Kettering 

Cancer Center 

New York, New York 

PPrithviRaj,MD 

Medical Director 

The National Pain Institute 

of Georgia 

Clinical Professor of 

Anesthesiology 

The Medical College of Georgia 

Atlanta, Georgia 

David W. Rattner, MD, FACS 
Associate Professor of Surgery 
Harvard Medical School 
Boston, Massachusetts 

L. Brian Ready, MD, FRCP(C) 
Professor of Anesthesiology 
Director, Acute Pain Service 
University of Washington 
Medical Center 
Seattle, Washington 

Marjorie Ream, RN, MN, OCN 
Vice President 
Hospice Services, Inc. 
Butler, Pennsylvania 






210 






Contributors 



Patrick M. Renfro, RN, MS, CRC 
Rehabilitation Nurse/Counselor 
Renfro & Associates 
Littleton, Colorado 

Linda Jo Rice, MD 
Director of Anesthesia Research 
Hartford Hospital and 
Newington Children's Hospital 
Hartford, Connecticut 

Anthony J. Richtsmeier, MD 
Director, Section of 
Behavioral Pediatrics 
Rush-Presbyterian-St. Luke's 
Medical Center 
Chicago, Illinois 

Margaret E. Rinehart, MS, PT 
Assistant Professor 
Thomas Jefferson University 
Philadelphia, Pennsylvania 

Patricia L. Roberts, MD 
Staff Surgeon 
Department of 
Colon-Rectal Surgery 
Lahey Clinic 
Burlington, Massachusetts 

Susan Howell Robinson, RN, 
MS, OCN 

Oncology Clinical Nurse Specialist 
Massey Cancer Center 
Medical College of Virginia 
Richmond, Virginia 

Michael G. Rock, MD 
Associate Professor of 
Orthopedic Surgery 
Mayo Clinic 
Rochester, Minnesota 

John Rogers, MD, MPH 
Associate Professor of 
Family Medicine 
Baylor College of Medicine 
Houston, Texas 



Charles Rosenbaum, MD 
Director, Oncology Clinic 
Assistant Medical Director 
Marlborough Hospital 
Marlborough, Massachusetts 

Hubert L. Rosomoff, MD, 
DMedSc 

Professor and Chairman 
Department of 
Neurological Surgery 
University of Miami 
Medical Director 
Comprehensive Pain and 
Rehabilitation Center 
Miami, Florida 

David A. Rothenberger, MD 
Clinical Professor and Chief 
Division of 

Colon and Rectal Surgery 
Department of Surgery 
University of Minnesota 
St. Paul, Minnesota 

B. W. Ruffner, Jr., MD, FACP 
Practicing Medical Oncologist 
Baronness Erlanger Hospital 
Chattanooga, Tennessee 

Patricia Rushton, RN, PhD 
Oncology Clinical Specialist 
VA Medical Center 
Salt Lake City, Utah 

Paula Sallmen, RN, BAN, OCN 
Program Director 
Virginia Piper Cancer Institute 
Abbott Northwestern Hospital 
Minneapolis, Minnesota 



211 



Management of Cancer Pain 



Marilyn C. Savedra, RN, DNS, 

FAAN 

Professor and Acting Chair 

University of California, 

San Francisco 

School of Nursing 

Department of 

Family Health Care Nursing 

San Francisco, California 

Neil L. Schechter, MD 

Professor of Pediatrics 

University of Connecticut 

Department of Pediatrics 

St. Francis Hospital and Medical 

Center 

Hartford, Connecticut 

Betty L. Schmoll, RN, MS 
President and CEO 
Hospice of Dayton, Inc. 
Dayton, Ohio 

Florence Seelig, RN, OCN 
Oregon Health Sciences 
University 
Portland, Oregon 

Mary S. Sheridan, PhD, ACSW 
Director of Social Services 
Pali Momi Medical Center 
Aiea, Hawaii 

Andrew G. Shetter, MD, FACP 
Chief, Section of Functional and 
Sterotactic Neurosurgery 
Barrow Neurological Institute 
Phoenix, Arizona 

Mary A. Simmonds, MD 

Clinical Assistant Professor 

of Medicine 

Milton S. Hershey 

Medical Center 

Camp Hill, Pennsylvania 



Marybeth Singer, RN, BSN, OCN 
Nursing Supervisor 
Dana Farber Cancer Institute 
Boston, Massachusetts 

Albert L. Siu, MD, MSPH 
Assistant Professor 
University of California, 
Los Angeles 
Department of Medicine 
Los Angeles, California 

Thomas J. Smith, MD, FACP 
Assistant Professor of Medicine 
and Health Administration 
Massey Cancer Center 
Medical College of Virginia 
Richmond, Virginia 

William J. Spanos, Jr., MD, FACR 

Professor and Vice Chairman 

Department of 

Radiation Oncology 

University of Louisville 

School of Medicine 

James Graham Brown Cancer 

Center 

Louisville, Kentucky 

Judith A. Spross, MS, RN, OCN, 

FAAN 

Oncology Nurse Consultant 

Boston, Massachusetts 

Michael D'Arcy Stanton-Hicks, 

MB, DrMed, FFARCS 

Director, 

Pain Management Center 

Cleveland Clinic Foundation 

Cleveland, Ohio 

Alan D. Steinfeld, MD, FACR 
Associate Professor of Radiology 
New York University 
Medical Center 
New York, New York 



212 



Contributors 



Porter Storey, MD 
Medical Director 
The Hospice at the 
Texas Medical School 
Houston, Texas 

Carol J. Swenson, RN, MS, OCN 
Oncology Clinical Nurse Specialist 
Swedish American Hospital 
Rockford, Illinois 

Karen L. Syrjala, PhD 
Psychological Services Director 
Pain & Toxicity Program 
Fred Hutchinson Cancer 
Research Center 
Seattle, Washington 

Dennis C. Turk, PhD 
Professor, Psychiatry, 
Anesthesiology & 
Behavioral Science 
University of Pittsburgh 
School of Medicine 
Pain Evaluation and 
Treatment Institute 
Pittsburgh, Pennsylvania 

Claudette Varricchio, RN, DSN, 
OCN, FAAN 
Program Director/ 
Nurse Consultant 
National Cancer Institute 
Bethesda, Maryland 

Sridhar V. Vasudevan, MD 
Clinical Professor of Physical 
Medicine and Rehabilitation 
Medical Director 
Pain Rehabilitation Center 
Elmbrook Memorial Hospital 
Brookfield, Wisconsin 

Sandra Ward, RN, PhD 
Assistant Professor 
University of Wisconsin-Madison 
School of Nursing 
Madison, Wisconsin 



Carol A. Warfield, MD 

Assistant Professor of Anesthesia 

Harvard Medical School 

Director, 

Pain Management Center 

Beth Israel Hospital 

Boston, Massachusetts 

Andrew L. Warshaw, MD 
Harold and Ellen Danser 
Professor of Surgery 
Harvard Medical School 
Chief of General Surgery 
Massachusetts General Hospital 
Boston, Massachusetts 

Stuart Weiner, DO 

President 

Michigan Cancer Pain Initiative 

Flint, Michigan 

James Whitsitt, MSW 
Social Worker 

University of Iowa Hospitals 
and Clinics 
Iowa City, Iowa 

Rudolph M. Widmark, MD, PhD 

Medical Officer 

Food and Drug Administration, 

CDER 

Rockville, Maryland 

Elaine R. Williams, RN, MSW 

Regional Director 

Instructor 

Visiting Nurse Association/ 

Southeast Michigan 

Detroit, Michigan 

Melissa Wolff, MS, PT 

Coordinator, 

Pain Consultants Network 

University of Tennessee 

Medical Center 

Knoxville, Tennessee 



213 



Management of Cancer Pain 



Barbara Ann Wright, RPh 

Pharmacist 

Mid- America Cancer Center 

St. John's Regional 

Health Center 

Springfield, Missouri 

Geri Doran Yanes, MD 
Assistant Clinical Lecturer 
Department of 
Radiation Oncology 
University of Arizona 
Health Sciences Center 
Tucson, Arizona 

Donald M. Yealy, MD, FACEP 
Assistant Professor 
Department of 
Emergency Medicine 
Texas A&M University 
Health Sciences Center 
Temple, Texas 



Lonnie Zeltzer, MD 
Professor of Pediatrics 
Director, University of 
California, Los Angeles 
Pediatric Pain Program 
Departments of Anesthesiology 
and Pediatrics 
University of California, 
Los Angeles 
School of Medicine 
Los Angeles, California 






214 






Contributors 



List of Site Testers 

Anne E. Belcher, PhD 
Associate Professor and Chair 
University of Maryland 
School of Nursing 
Baltimore, Maryland 

JoAnn Dalton, RN, EdD 
Associate Professor 
University of North Carolina 
at Chapel Hill, 
School of Nursing 
Chapel Hill, North Carolina 

Marion B. Dolan, RN 

President 

Heritage Home Health 

Merideth, New Hampshire 

Marilee Donovan, RN, PhD 
Associate Hospital Director 
Oregon Health Sciences 
University 
Portland, Oregon 

Thomas E. Elliott, MD 
Director of 

Education and Research 
Duluth Clinic 
Duluth, Minnesota 

Walter B. Forman, MD, FACP 

Associate Chief of Staff 
Geriatrics/Extended Care Service 
Associate Professor, 
Medicine, Geriatrics 
VA Medical Center 
Albuquerque, New Mexico 

Marvin Frederickson, MD 

Medical Oncology Section 

Medical Director of 

Group Health Hospice Program 

Group Health Cooperative of 

Puget Sound 

Seattle, Washington 



Stephen A. Gudas, PT, PhD 
Assistant Professor 
Departments of Rehabilitation 
Medicine and Anatomy 
Medical College of Virginia 
Richmond, Virginia 

Linda U. Krebs, RN, MS, OCN 
Nursing Oncology 
Program Leader 
University of Colorado 
Cancer Center 
Denver, Colorado 

Jacqueline A. LaPerriere, RPh 
Pain Service Coordinator 
H. Lee Moffitt Cancer Center 
Tampa, Florida 

Michael H. Levy, MD, PhD 

Co-Director, 

Pain Management Center 
Fox Chase Cancer Center 
Philadelphia, Pennsylvania 

Jean B. Moen, RN, MS 
Senior Vice-President, 
Operations 

American Cancer Society 
Georgia Division 
Atlanta, Georgia 

Maryann R. Nalley, BS, RN 

Director of Professional 

Education 

American Cancer Society 

Missouri Division 

Jefferson City, Missouri 



215 



Management of Cancer Pain 

David C. Pederson, CRNA 
American Association of Nurse 
Anesthetists 
Carroll, Iowa 

Jeaneva Reese, BA 
Staff Assistant, Nursing 
Research Division 
Harbor-University of California, 
Los Angeles, Medical Center 
Torrance, California 

Patrick M. Renfro, RN, MS, CRC 
Rehabilitation Nurse/Counselor 
Renfro & Associates 
Littleton, Colorado 



216 



Organizations and Individuals 
Providing Additional Scientific, 
Technical, and Administrative Support: 



Johns Hopkins University 
Baltimore, Maryland 

Janice Fitzgerald Ulmer, RN, PhD, 
Project Manager 
Donna Mahrenholz, RN, PhD, 
Dorothy Herron, RN, MSN 
Joyce S. Willens, RN, MSN 
Yeonghee Shin, PhD 
Patricia Stephens, PhD 
Leslie C. Dunham, BA 

Harvard University 
Massachusetts General Hospital 
Boston, Massachusetts 

Jane Ballantyne, MB, BS 
Elon Eisenberg, MD 
Evelyn Hall 

University of Texas 

MD Anderson Cancer Center 

Guadalupe Palos, MSW, RN, 
OCN, CSW 



Agency for Health Care Policy 
and Research 
Rockville, Maryland 

Kathleen McCormick, PhD, RN 
Carole Hudgings, RN, PhD 
Margaret Coopey, RN, MS 
Karen Carp 
Randie Siegel 

EEI 

Alexandria, Virginia 

Martha Sencindiver 

Mikalix and Company 
Waltham, Massachusetts 

Sharon Sokoloff 

Other individuals 

Valerie Exar 
Marsha Whitson 



217 



Attachment A. 

Tables of Scientific Evidence 

A1 . Scientific evidence for pain reduction in adults 
A2. Scientific evidence for pain reduction in children 



219 



Explanation of Table of Evidence 

The following tables summarize the scientific evidence for inter- 
ventions to manage pain. The evidence is classified by type and 
strength. The type of evidence for recommendations is ordinally 
ranked in categories from I to V. I is evidence from metaanalysis of 
multiple, well-designed controlled studies. II through V are evidence 
obtained from experimental studies (II) through case reports and clin- 
ical examples (V). Evidence is further subdivided according to 
whether the studies were conducted on patients with cancer or on 
other clinical populations. The column in the table labeled "Type of 
Evidence" summarizes the types of evidence that support interven- 
tions discussed in the guideline. The strength and consistency of 
evidence are described in the text. 

Briefly, the strength and consistency of evidence for recommenda- 
tions summarize the evidence and note whether the evidence is gener- 
ally consistent or inconsistent. Strength of evidence ranges from A, 
which is the strongest evidence, to D, which indicates that there is 
little or no evidence or evidence of type V only. The strength of 
recommendation is summarized in the column of the tabled labeled 
"Strength and Consistency of Evidence." 

When the strength of evidence is A or B, the panel's recommenda- 
tions are based primarily on the evidence. When the strength of 
recommendation is C or D, the panel used the available empirical 
evidence but based their recommendations primarily on expert judg- 
ment. The term "panel consensus" is used when the recommendation 
is a statement of panel opinion regarding desirable practice and there 
is evidence that the practice is not commonly being followed. 

Two tables are provided. Table Al summarizes the scientific 
evidence for the management of pain in adult populations. Table A2 
summarizes the scientific evidence for the management of pain in 
children and adolescents. 



221 



A1 . Scientific evidence for pain reduction in adults 



Intervention 




Type of evidence 


Strength and 
consistency 
of evidence 




Cancer 
patients 


Other 
patients 


Pharmacologic interventions 


Acetaminophen 
and NSAIDs 


Oral (alone) 


la 


lb 


A 


Oral (adjunct to opioid) 


lla 


lb 


A 


Rectal 




lib, 1Mb 


B 


Parenteral (ketorolac) 


la 


lb 


A 


Opioids 


Oral 


la 


lb 


A 


Controlled release 


la 




A 


Rectal 


Ilia, IVa 


lib 


B 


Transdermal 


Ilia, Va 


lib 


B 


Intramuscular (IM) 


lla 


lb 


A 


Subcutaneous (SC) 


lla 


lb 


A 


Intravenous (IV) 


lla 


lb 


A 


PCA (IV and SC) 


la 


lb 


A 


Epidural and intrathecal 


lla, Ilia 


lb, 1Mb 


A 


Intracerebral ventricular 


lla, Ilia, IVa 




A 


Local anesthetics 


Oral 
Topical 
Systemic 


lla 


lib 


B 
B 


Intravenous 


IVa 




C 


Epidural and intrathecal 


IVa 


lb 


A 


Interpleural 


Va 


lib, Mb, Vb 


B 


Inhalent analgesia 


Nitrous oxide 


Va 


lib, 1Mb 


C 


Adjuvant analgesics 


Corticosteroids 


lla 


lib, 1Mb, IVb 


B 


Anticonvulsant agents 


Ilia 


lib, 1Mb, IVb 


B 


Antidepressants 


lla, Ilia 


lb, lib, lllb, IVb 


A 


Neuroleptics 


lla 


lib 


C 


Hydroxyzine 


Ilia 


Mb 


C 


Psychostimulants 


lla, Va 


lib 


D 


Calcitonin 


lla, Ilia, Va 




C 


Bisphosphonates 


lla, Ilia 




C 


Nonpharmacologic interventions: invasive 


Surgery 


Excision or debulking 
of primary tumor or 
metastasis 


Ilia, Va 




D 


Neurosurgery 


Peripheral neurectomy 


Va 




D 


Dorsal rhizotomy 


IVa, Va 




B 


Comissural myelotomy or 
cordotomy 


IVa, Va 




B 


Hypophysectomy 


IVa, Va 




B 



222 



Intervention 




Type of evidence 


Strength and 
consistency 
of evidence 




Cancer 
patients 


Other 
patients 


Nonpharmacologic interventions: invasive (continued) 


Neuroaugmentation 


Deep brain stimulation 


IVa, Va 




B 


Spinal cord stimulation 


IVa, Va 




C 


Neurolytic blocks 


Celiac 


HaJlla.lVa 


Illb.lVb 


A 


Hypogastric 


IVa, Va 




B 


Intratheca 
Epidural 


Ilia, Va 
Va 




B 
D 


Trigeminal 


Va 


IVb, Vb 


B 


Peripheral 
intercostal 


Va 




D 


Radiotherapy 


Local field 


lla 




B 


Wide field 


lla 




B 


Fractionation: 
Single dose 


lla 




B 


Multidose 


lla 




B 


Brachytherapy 


Ilia 




B 


0-emitting 
radiopharmaceuticals 


la, lla, Ilia 




A 


Psychosocial 


Education: 
Pain management 


lla, Ilia 




B 


Providing sensory and 
procedural information 




lb 


A 


Reframing/cognitive 
reappraisal 


lla, Va 


lib 


B 


Distraction including music 


lla, Ilia, Va 


lib, lllb 


B 


Relaxation, imagery 


lla, IVa 


lb 


A 


Biofeedback 


Ilia, Va 


lib, lllb 


B 


Psychotherapy and 
structured support 


lla, Va 




B 


Hypnosis 


la, lla, Va 




A 


Physical 
therapeutic 


Superficial heat 


IVa, Va 




D 


Superficial cold 


Va 




D 


Massage 


lla, IVa 




D 


Active and passive exercise 


Va 


lllb, IVb 


B 


Immobilization 


Va 




D 


Counterstimulation 


Transcutaneous electrical 
nerve stimulation (TENS) 


IVa, Va 


lb 


C 


Acupuncture 


IVa, Va 


lib, lllb, IVb, Vb 


C 



223 



A2. Scientific evidence for pain reduction in children 



Intervention 




Type of evidence 


Strength and 
consistency 
of evidence 




Cancer 
patients 


Other 
patients 


Pharmacologic interventions 


Acetaminophen 
and NSAIDs 


Oral (alone) 




lib 


D 


Rectal 




lib 


B 


Parenteral (ketorolac) 




lib 


A 


Opioids 


Oral 


Ilia 


Mb 


D 


Rectal 


— 


lib 


D 


Transdermal 


IVa 


— 


D 


Intramuscular (IM) 


— 


Mb 


B 


Subcutaneous (SC) 


IVa 




D 


Intravenous (IV) 


Ma 


lla 


A 


PCA (IV and SC) 


lla 


lib 


B 


Epidural and intrathecal 


IVa 


lib 


A 


Local anesthetics 


Infiltration 




lib 


B 


Epidural and intrathecal 


Va 


lib 


A 


Interpleural 




lib 


C 


Inhalent analgesia 


Nitrous oxide 


Va 


1Mb 


D 


Topical anesthetics 


Emulsion of 

local anesthetics (EM LA) 


lla 


lib 


A 


Other 




lib 


B 


Adjuvant analgesic 


Psychostimulants 


IVa 




D 


Nonpharmacologic interventions; noninvasive 


Psychosocial 


General preparation 1 


IVa 


lib 


B 


Providing sensory and 
procedural information 


lla 


lib 


B 


Distraction including music 


lla 


lib 


C 


Relaxation 




lib 


B 


Biofeedback 




lib 


D 


Hypnosis/imagery 


lla 


lib 


B 


Parent presence 


lla 


lib 


B 


Counterstimulation 


Transcutaneous electrical 
nerve stimulation (TENS) 


Va 




D 



1 Many of these general preparation studies were done in the 1960s to early 1980s. Few of 
these studies used self-report of pain. Most studies look at behavior, upset, distress, anxiety, 



and physiologic outcomes. 



224 



Type of evidence 

I. Meta-analysis of multiple, well-designed controlled studies. 

a. Studies of patients with cancer. 

b. Studies of other clinical populations. 

II. At least one well-designed experimental study. 

a. Studies of patients with cancer. 

b. Studies of other clinical populations. 

III. Well-designed, quasiexperimental studies such as nonrandomized controlled, 
single group pre-post, cohort, time series, or matched case-controlled stud- 
ies. 

a. Studies of patients with cancer. 

b. Studies of other clinical populations. 

IV. Well-designed nonexperimental studies, such as comparative and correla- 
tional descriptive and case studies. 

a. Studies of patients with cancer. 

b. Studies of other clinical populations. 

V. Case reports and clinical examples. 

a. Studies of patients with cancer. 

b. Studies of other clinical populations. 

Strength and consistency of evidence 

A. There is evidence of type I or consistent findings from multiple studies of types 
II, III, or IV. 

B. There is evidence of types II, III, or IV, and findings are generally consistent. 

C. There is evidence of types II, III, or IV, but findings are 
inconsistent. 

D. There is little or no evidence, or there is type V evidence only. 

Panel Consensus — Practice recommended on the basis of opinion of experts in 
pain management. 



225 



Attachment B. 

Pain assessment and management instruments 

Pain Assessment Instruments for Adults 

B1 . Brief Pain Inventory (Short Form) 

B2. Initial Pain Assessment Tool 

B3. Pain Distress Scales 

B4. The Memorial Pain Assessment Card 

Pain Assessment Instruments for Children 

B5. Pain Experience History 

B6. Eland Color Scale Figures 

B7. Poker Chip Tool Instructions Sheet 

B8. Word-Graphic Rating Scale 

B9. Pain Affect Faces Scale 

Instruments for Pain Management Documentation 

B10. Pain Management Log 

B1 1 . Flowsheet for Pain Management Documentation 



227 



B1 . Brief Pain Inventory (Short Form) 



Study ID#. 



Hospital#. 



Do not write above this line 



Date: /_ 

Time: 



Name: 



Last 



First 



Middle Initial 



1 ) Throughout our lives, most of us have had pain from time to time (such as 
minor headaches, sprains, and toothaches). Have you had pain other than 
these everyday kinds of pain today? 1 . Yes 2. No 

2) On the diagram, shade in the areas where you feel pain. Put an X on the 
area that hurts the most. 



Right 




Left Left 




Right 



3) 


Please rate your pain by circling the one number that best describes your 
pain at its worst in the past 24 hours. 


0123456789 10 
No Pain as bad as 
pain you can imagine 


4) 


Please rate your pain by circling the one number that best describes your 
pain at its least in the past 24 hours. 




0123456789 10 
No Pain as bad as 
pain you can imagine 



5) Please rate your pain by circling the one number that best describes your 
pain on the average. 





No 

pain 



1 




8 9 10 

Pain as bad as 

you can imagine 



228 



6) Please rate your pain by circling the one number that tells how much pain 
you have right now. 





No 

pain 



8 9 10 

Pain as bad as 

you can imagine 



7) What treatments or medications are you receiving for your pain? 



8) 



9) 



In the past 24 hours, how much relief have pain treatments or medications 
provided? Please circle the one percentage that most shows how much 
relief you have received. 



0% 
No 
relief 



10% 20% 30% 40% 50% 60% 70% 



80% 90% 100% 
Complete 
relief 



Circle the one number that describes how, during the past 24 hours, pain 
has interfered with your: 

A. General activity 



1 

Does not 
interfere 



9 10 

Completely 

interferes 



B. Mood 






12 3 4 5 6 7 

Does not 

interfere 


8 


9 10 

Completely 

interferes 


C. Walking ability 


12 3 4 5 6 7 

Does not 

interfere 


8 


9 10 

Completely 

interferes 


D. Normal work (includes both work outside the home and housework) 


12 3 4 5 6 7 

Does not 

interfere 


8 


9 10 

Completely 

interferes 


E. Relations with other people 


12 3 4 5 6 7 

Does not 

interfere 


8 


9 10 

Completely 

interferes 


F. Sleep 


12 3 4 5 6 7 

Does not 

interfere 


8 


9 10 

Completely 

interferes 


G. Enjoyment of life 


1 2 3 4 5 6 7 

Does not 

interfere 


8 


9 10 

Completely 

interferes 



Source: Pain Research Group, Department of Neurology, University of Wisconsin-Madison. 
Used with permission. May be duplicated and used in clinical practice. 



229 



B2. Initial Pain Assessment Tool 



Patient's name 
Diagnosis 



Date 

_Age Room. 



Physician. 
Nurse 



Location: Patient or nurse marks drawing. 




II. Intensity: Patient rates the pain. Scale used. 

Present: 



Worst pain gets:. 
Best pain gets:_ 



Acceptable level of pain:. 



III. Quality: (Use patient's own words, e.g., prick, ache, burn, throb, pull, sharp) 



IV. Onset, duration, variations, rhythms: 



V. Manner of expressing pain: 

VI. What relieves the pain? 



VII. What causes or increases the pain? 

VIII. Effects of pain: (Note decreased function, decreased quality of life.) 

Accompanying symptoms (e.g., nausea) 

Sleep 

Appetite 

Physical activity 

Relationship with others (e.g., irritability) 

Emotions (e.g., anger, suicidal, crying) 

Concentration 

Other 



IX. Other comments: 









X. Plan: 



Note: May be duplicated and used in clinical practice. 
Source: McCaffery and Beebe, 1989. Used with permission. 

230 



B3. Pain Distress Scales 



Simple Descriptive Pain Distress Scale 1 

None Annoying Uncomfortable Dreadful Horrible Agonizing 



No 
pain 



0-10 Numeric Pain Distress Scale 1 

Distressing 
pain 

— I — I — I — I — I — I- 

3 4 5 6 7 8 



Unbearable 
pain 



10 



No 
distress 



Visual Analog Scale (VAS) : 



Unbearable 
distress 



1 lf used as a graphic rating scale, a 10 cm baseline is recommended. 
2 A 10-cm baseline is recommended for VAS scales. 
Source: Acute Pain Management Guideline Panel, 1992. 



231 



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c 
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^_ 
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LJJ 







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(0 

o 






c 
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*s 






(0 
(0 


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(0 


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0. 








!s 




"55 "o 


'C 




£ o 


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o o 


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o 




§E 


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■ 






a 










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g-CD CO 



(0 

o 

<D 

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■M £ 

eg. 

£"6 



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£2:9 £ 

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(0 

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(0 



CD 
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CD 


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CD 


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ca 


u_ 


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a> 


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£2 


■M 


3 


o 


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05 



232 



B5. Pain experience history 



Child form 


Parent form 


Tell me what pain is. 


What word(s) does your child 
use in regard to pain? 


Tell me about the hurt you have 
had before. 


Describe the pain experiences 
your child has had before. 


Do you tell others when you hurt? 
If yes, who? 


Does your child tell you or 
others when he/she is hurting? 


What do you do for yourself 
when you are hurting? 


How do you know when your 
child is in pain? 


What do you want others to do 
for you when you hurt? 


How does your child usually 
react to pain? 


What don't you want others to do 
for you when you hurt? 


What do you do for your child 
when he/she is hurting? 


What helps the most to take 
your hurt away? 


What does your child do for 
him/herself when he/she is hurting? 


Is there anything special that 
you want me to know about you 
when you hurt? (If yes, have 
child describe.) 


What works best to decrease or 
take away your child's pain? 




Is there anything special that 
you would like me to know 
about your child and pain? 
(If yes, describe.) 



Adapted with permission from Hester and Barcus, 1986. 



233 



B6. Eland Color Scale: Directions for Use 



After discussing with the child several things that have hurt the child in the past: 

1 . Present eight crayons or markers to the child. Suggested colors are yellow, 
orange, red, green, blue, purple, brown, and black. 

2. Ask the following questions, and after the child has answered, mark the appro- 
priate square on the tool (e.g., severe pain, worst hurt), and put that color away 
from the others. For convenience, the word hurt is used here, but whatever 
term the child uses should be substituted. Ask the child these questions: 

■ "Of these colors, which color is most like the worst hurt you have ever had 
(using whatever example the child has given) or the worst hurt anybody 
could ever have?" Which phrase is chosen will depend on the child's 
experience and what the child is able to understand. Some children may 
be able to imagine much worse pain than they have ever had, while other 
children can only understand what they have experienced. Of course, 
some children may have experienced the worst pain they can imagine. 

■ "Which color is almost as much hurt as the worst hurt (or use example 
given above, if any), but not quite as bad?" 

■ "Which color is like something that hurts just a little?" 

■ "Which color is like no hurt at all?" 

3. Show the four colors (marked boxes, crayons, or markers) to the child in the 
order he has chosen them, from the color chosen for the worst hurt to the color 
chosen for no hurt. 

4. Ask the child to color the body outlines where he hurts, using the colors he has 
chosen to show how much it hurts. 

5. When the child finishes, ask the child if this is a picture of how he hurts now or 
how he hurt earlier. Be specific about what earlier means by relating the time to 
an event, e.g., at lunch or in the playroom. 



Reprinted with permission of J.M. Eland from McCaffery and Beebe, 1989. May be duplicated 
for use in practice. 



234 



Eland Color Scale: Figures 



Mark each box with the color the child selects. 



No pain 
No hurt 



Mild pain 
A little hurt 



Moderate pain 
More hurt 



Severe pain 
Worst hurt 




235 



B7. Poker Chip Tool Instruction Sheet 1 



English Instructions: 

1 . Say to the child: "I want to talk with you about the hurt you may be having 
right now. " 

2. Align the chips horizontally in front of the child on the bedside table, a clip- 
board, or other firm surface. 

3. Tell the child, "These are pieces of hurt. " Beginning at the chip nearest the 
child's left side and ending at the one nearest the right side, point to the chips 
and say, "This (first chip) is a little bit of hurt and this (fourth chip) is the most 
hurt you could ever have. " 

For a young child or for any child who may not fully comprehend the instruc- 
tions, clarify by saying, "That means this (one) is just a little hurt, this (two) is a 
little more hurt, this (three) is more yet, and this (four) is the most hurt you could 
ever have. " 

■ Do not give children an option for zero hurt. Research with the Poker Chip 
Tool has verified that children without pain will so indicate by responses 
such as, "I don't have any." 

4. Ask the child, "How many pieces of hurt do you have right now?" 

■ After initial use of the Poker Chip Tool, some children internalize the 
concept "pieces of hurt." If a child gives a response such as "I have one 
right now," before you ask or before you lay out the poker chips, proceed 
with instruction #5. 

5. Record the number of chips on the Pain Flow Sheet. 

6. Clarify the child's answer by words such as, "Oh, you have a little hurt? 
Tell me about the hurt." 



Spanish Instructions 2 : 

1 . Tell the parent: "Estas fichas de poker son una manera de medir dolor. Usamos 
cuatro fichas rojas. " 

2. Say to the child: "Las fichas son como pedazos de dolor: una ficha (pedazo) es 
un poquito de dolor, mientras cuatro fichas (pedazos) significa el dolor maximo 
que tu puedes sentir. iCuantos pedazos de dolor tienes?" 

1 Developed in 1 975 by Nancy O. Hester, University of Colorado Health Sciences Center, 
Denver, CO. 

2 Spanish instructions by Jordan-Marsh, M., Hall, D., Yoder, L, Watson, R., McFarlane-Sosa, 
G., & Garcia, M. (1990). The Harbor-UCLA Medical Center Humor Project for Children. Los 
Angeles: Harbor-UCLA Medical Center. 



236 



B8. Word-Graphic Rating Scale 



Instructions 

"This is a line with words to describe how much pain you may have. This side of the 
line means no pain and over here the line means worst possible pain. " (Point with 
your finger where "no pain" is, and run your finger along the line to "worst possible 
pain," as you say it.) "If you have no pain, you would mark like this." (Show exam- 
ple.) "If you have some pain, you would mark somewhere along the line, depending 
on how much pain you have." (Show example.) "The more pain you have, the closer 
to worst pain you would mark. The worst pain possible is marked like this. " (Show 
example.) 

"Show me how much pain you have right now by marking with a straight, up and 
down line anywhere along the line to show how much pain you have right now. " 



1 

No 

pain 


Little 
pain 


Medium 
pain 


Large 
pain 


1 

Worst 
possible 
pain 



Reprinted with permission from Savedra, Tesler, Holzemer, et al., 1989. [updated 1992] 



237 



B9. Pain Affect Faces Scale 




Children are presented with one of three different randomly ordered face sheets. 
They select the face that best represents how they feel in relation to their pain 
conditions from "the happiest feeling possible" to the "saddest feeling possible." 
This figure is actually the scoring card used to quantify children's responses. The 
numbers represent the magnitude of pain affect (between and 1) shown in each 
face, based on previous research on children. 



Reprinted with permission of McGrath from Patt, 1993. 



238 



B10. Pain management log 



Pain management log for 



Please use this pain assessment scale to fill out your pain control log: 

01 23456789 10 



2 3 4 5 

H — I — I — f- 



No 
pain 



i — I — I — I 



Worst 
pain 



Date 


Time 


How 
severe is 
the pain? 


Medicine or 

non-drug 

pain control 

method 


How 
severe is 
the pain 
after one 

hour? 


Activity at 
time of pain 







































































































































































































































239 



B1 1. Flowsheet for pain management documentation 



Patient 



Date 



Pain rating scale used 1 . 



Purpose: To evaluate the safety and effectiveness of the analgesic(s) 
Analgesics(s) prescribed: 



Time 


Pain 
rating 


Analgesic 


R 


P 


BP 


Level of 
arousal 


Other 2 


Plan and 
comments 

























































































































































































































































































































































Source: McCaffery & Beebe, 1989. Used with permission. 
Note: May be duplicated for use in clinical practice. 

1 Pain rating: A number of different scales may be used. Indicate which scale is used and use 
the same scale each time. 

2 Possibilities for other columns: bowel function, activities, nausea and vomiting, and other 
pain relief measures. Identify the side effects of greatest concern to patient, family, physician, 
and nurse. 



240 



Attachment C. 

Sample relaxation exercises 

Exercise 1 . Slow rhythmic breathing for relaxation 
Exercise 2. Simple touch, massage, or warmth for relaxation 
Exercise 3. Peaceful past experience 
Exercise 4. Active listening to recorded music 



241 



Exercise 1 : Slow rhythmic breathing for relaxation 



1 . Breathe in slowly and deeply. 

2. As you breathe out slowly, feel yourself beginning to relax; feel the tension 
leaving your body. 

3. Now breathe in and out slowly and regularly, at whatever rate is comfortable 
for you. You may wish to try abdominal breathing. 

4. To help you focus on your breathing and breathe slowly and rhythmically: (a) 
breathe in as you say silently to yourself, "in, two, three"; (b) breathe out as you 
say silently to yourself, "out, two, three." 

or 

Each time you breathe out, say silently to yourself a word such as "peace" 
or "relax." 

5. Do steps 1 through 4 only once or repeat steps 3 and 4 for up to 20 minutes. 

6. End with a slow deep breath. As you breathe out say to yourself, "I feel alert 
and relaxed." 

Source: McCaffery and Beebe, 1989. Adapted and reprinted with permission. 
Note: May be duplicated for use in clinical practice. 



242 



Exercise 2. Simple touch, massage, or warmth for relaxation 

Touch and massage are age-old methods of helping others relax. 
Some examples are: 

(1) Brief touch or massage, e.g., handholding or briefly touching or rubbing a 
person's shoulder. 

(2) Warm foot soak in a basin of warm water, or wrap the feet in a warm, wet 
towel. 

(3) Massage (3 to 1 minutes) may consist of whole body or be restricted to back, 
feet, or hands. If the patient is modest or cannot move or turn easily in bed, 
consider massage of the hands and feet. 

■ Use a warm lubricant, e.g., a small bowl of hand lotion may be warmed in 
the microwave oven, or a bottle of lotion may be warmed by placing it in a 
sink of hot water for about 1 minutes. 

■ Massage for relaxation is usually done with smooth, long, slow strokes. 
(Rapid strokes, circular movements, and squeezing of tissues tend to 
stimulate circulation and increase arousal.) However, try several degrees 
of pressure along with different types of massage, e.g., kneading, 
stroking, and circling. Determine which is preferred. 

Especially for the elderly person, a back rub that effectively produces relaxation 
may consist of no more than 3 minutes of slow, rhythmic stroking (about 60 strokes 
per minute) on both sides of the spinous process from the crown of the head to the 
lower back. Continuous hand contact is maintained by starting one hand down the 
back as the other hand stops at the lower back and is raised. Set aside a regular 
time for the massage. This gives the patient something to look forward to and 
depend on. 



Source: McCaffery and Beebe, 1989. Adapted and reprinted with permission. 
Note: May be duplicated for use in clinical practice. 



243 



Exercise 3. Peaceful past experiences 



Something may have happened to you a while ago that brought you peace and 
comfort. You may be able to draw on that past experience to bring you peace or 
comfort now. Think about these questions: 

1 . Can you remember any situation, even when you were a child, when you felt 
calm, peaceful, secure, hopeful, or comfortable? 

2. Have you ever daydreamed about something peaceful? What were you 
thinking of? 

3. Do you get a dreamy feeling when you listen to music? Do you have any 
favorite music? 

4. Do you have any favorite poetry that you find uplifting or reassuring? 

5. Have you ever been religiously active? Do you have favorite readings, hymns, 
or prayers? Even if you haven't heard or thought of them for many years, child- 
hood religious experiences may still be very soothing. 

Additional points: Very likely some of the things you think of in answer to these 
questions can be recorded for you, such as your favorite music or a prayer. Then, 
you can listen to the tape whenever you wish. Or, if your memory is strong, you 
may simply close your eyes and recall the events or words. 



Source: McCaffery and Beebe, 1989. Adapted and reprinted with permission. 
Note: May be duplicated for use in clinical practice. 



244 



Exercise 4. Active listening to recorded music 

1 . Obtain the following: 

■ A cassette player or tape recorder. (Small, battery-operated ones are 
more convenient.) 

■ Earphone or headset. (This is a more demanding stimulus than a speaker 
a few feet away, and it avoids disturbing others.) 

■ Cassette of music you like. (Most people prefer fast, lively music, but 
some select relaxing music. Other options are comedy routines, sporting 
events, old radio shows, or stories.) 

2. Mark time to the music, e.g., tap out the rhythm with your finger or nod your 
head. This helps you concentrate on the music rather than your discomfort. 

3. Keep your eyes open and focus steadily on one stationary spot or object. If 
you wish to close your eyes, picture something about 

the music. 

4. Listen to the music at a comfortable volume. If the discomfort increases, try 
increasing the volume; decrease the volume when the discomfort decreases. 

5. If this is not effective enough, try adding or changing one or more of the 
following: massage your body in rhythm to the music; try other music; mark 
time to the music in more than one manner, e.g., tap your foot and finger at the 
same time. 

Additional points: Many patients have found this technique to be helpful. It tends 
to be very popular, probably because the equipment is usually readily available and 
is a part of daily life. Other advantages are that it is easy to learn and is not physi- 
cally or mentally demanding. If you are very tired, you may simply listen to the 
music and omit marking time or focusing on a spot. 



Source: McCaffery and Beebe, 1989. Adapted and reprinted with permission. 
Note: May be duplicated for use in clinical practice. 



245 



Index 



A 

Abdominal pain 
causes of, 36 
diagnosis of, 36-37 
Ablative surgery 

advantages and disadvantages 

of, 43 
description of, 100-101 
explanation of, 185 
Abstinence syndrome, 50-51 
Acetaminophen (APAP). 

See also NSAIDs 
advantages and disadvantages 

of, 42, 46 
dosing data for, 48, 49, 55 
recommendations for use of, 

39-41 
scientific evidence for, 222, 224 
used for children, 120-121 
used for elderly patients, 129 
used for neonates and 

infants, 124 
used with opioid analgesics, 

46, 53 
Acquired immunodeficiency 

syndrome (AIDS) 
delirium and, 134 
overview of, 139-140 
pain management in patients 

with, 1, 116, 140-141 
Acronyms list, 183 
Acupuncture 

advantages and disadvantages 

of, 45 
description of, 79-80, 185 
recommendations regarding, 

75, 76, 80 
scientific evidence for, 223 
Acute neuralgia, 33-34, 96 
Addiction. See also Substance 

abusing patients as defined 

in Controlled Substances 

Act, 18 
explanation of, 185 
fear of, 138, 141 
tolerance for opioids vs., 

39, 50-51, 135, 136 
Adjuvant analgesics. See also Analgesics; 

Anticonvulsants; 

Antidepressants; 

Bisphosphonates; Calcitonin; 

Corticosteroids; Hydroxyzine; 

Neuroleptic agents; Placebos 



to counteract side effects of 
opioids, 53 

description of, 65, 67-69 

dosing data for, 66 

explanation of, 65, 185 

NSAIDs used with, 46, 53 

recommendations for use of, 39, 40 

scientific evidence for, 222, 224 

used for children, 120-124 
Adolescents. See also Children 

pain in, 116-117 

patient-controlled analgesia for, 123 
AIDS. See Acquired immunodeficiency 

syndrome 
Alcohol 

drug interactions and, 70 

treatment with intraspinal, 96 
American Academy of Pediatrics, 112 
American Cancer Society (ACS), 86, 87 
American Self-Help Clearinghouse, 87 
Amitriptyline 

analgesic effects of, 67-68 

dosing data for, 66, 67 
Analgesics. See also Adjuvant analgesics; 
Drug therapy; Opioids 

administration methods for, 39, 
62, 126. See also specific 
methods 

advantages and disadvantages of, 42 

for postsurgical pain, 35 

principles of use of, 146 

for spinal cord compression pain, 31 

used for children, 120-124 

used for neonates and infants, 
124-125 
Anaprox (naproxen sodium), 48 
Anterolateral cordotomy, 100-101, 222 
Antiarrythmics, 66, 67 
Anticonvulsants 

advantages and disadvantages of, 44 

description of, 65, 67 

dosing data for, 66 
Antidepressants 

advantages and disadvantages of, 44 

dosing data for, 66 

use of, 67-68, 131 

used for children, 124 

used for elderly patients, 130 
Antidiuretic hormone secretion, 65 
Antiemetics, 63, 68, 92-93 
Antihistamines, 66 
Antineoplastic therapies, 70. See also 

Chemotherapy 
Antiviral therapy, 36 



247 



Management of Cancer Pain 



Anxiety, 133-134 
Anxiolysis, 185 
Anxiolytics 

explanation of, 185 

use of, 68, 110 
Arthropan (choline salicylate), 48 
Aspirin 

advantages and disadvantages of, 42 

dosing data for, 48, 55 

use of, 41, 46 

B 

Barbiturates 

long-term use of, 73 

for procedural pain, 111 
Behavioral observation 

of children, 119-120 

recommendations regarding, 115, 119 
Benzodiazepine, 73, 111, 113 
Biofeedback 

advantages and disadvantages of, 44 

explanation of, 185 

scientific evidence for, 223, 224 
Biologic therapy, 70 
Biopsies, 113 
Bisphosphonates, 69 
Bone marrow aspiration 

in children, 116 

procedural pain from, 113-114 
Bone marrow suppression, 65, 67 
Bone metastases 

diagnosis of, 30, 91 

epidural metastases as complication 
of, 30-31 

management of pain due to, 69 

radiation therapy for, 91-93 

recommendations regarding, 89 

to skull, 31, 32 
Brachytherapy, 94, 223 
Breakthrough pain, 185 
Brief Pain Inventory (Short Form), 

26, 228-229 
Brompton's cocktail, 73 
Bupivacaine, 95 
Buprenorphine, 50, 72 
Butorphanol 

description of, 50 

risks related to, 72, 73 

use of, 56 



c 

Caffeine, 53, 61 
Calcitonin, 69 
Cancer 

in minority patients, 138-139 
prevalence of and mortality from, 

hi, v, 7 
psychiatric problems associated with, 
130-134 
Cannabinoids, 72 
Carbamazepine 

description of, 65 
dosing data for, 66 
monitoring of patients receiving, 67 
Carprofen (Rimadyl), 48 
Celiac block, 97, 223 
Cervicomedullary junction 

myelotomy, 101 
Chemotherapy 

anticonvulsants in patients 

undergoing, 67 
depression and, 131 
description of, 70 

mucositis in patients undergoing, 37 
to treat Kaposi's sarcoma, 140 
Cheyne-Stokes respiratory patterns, 129 
Children. See also Adolescents; 
Infants; Neonates 
assessment of pain management 

strategies for, 127, 128 
drug monitoring in, 124 
drug side effects in, 124 
epidural analgesia for, 126 
HIV infection in, 140-141 
nonpharmacologic methods of pain 

management in, 126, 128 
opioid dosing data for, 52, 54. See 

also Opioids 
pain assessment in, 117-120 
pain in, 116-117 
pharmacologic methods of pain 

management in, 120-126, 128, 141 
procedural pain management in, 

107-114 
recommendations regarding 

assessment and treatment of, 115 
scientific evidence for pain reduction 
in, 224, 225 
Chloral hydrate, 108 
Chlorpromazine, 63, 73, 110 
Choline magnesium trisalicylate 
(Trilisate) 
dosing data for, 48 



248 



Index 



use of, 46-47 

used for children, 121 
Choline salicylate (Arthropan), 48 
Cisplatin, 34 
Clinical Practice Guideline for the 

Management of Cancer Pain 

methods used to develop, 20-21 

organization of, v, 2-5, 21 

purpose and goals of, iii, 1-2 
Clonazepam, 65 
Clonidine, 51 
Cocaine, 72 
Codeine 

description of, 49-50 

dosing data for, 52-55 

use of, 41, 45 

used for children, 123 

withdrawal symptoms from, 51 
Coexistent medical conditions 

drug therapy and, 70-71 

patient screening for, 89, 99 
Cognitive reappraisal 

explanation of, 185 

scientific evidence for, 223 
Cognitively impaired patients, 129 
Commissural myelotomy, 101, 222 
Confusion, 64 

Congnitively impaired patients, 115 
Conscious sedation 

explanation of, 185 

management of, 107, 112-113 
Constipation 

due to opioid use, 40, 61, 62 

management of, 61 
Controlled Substances Act (CSA), 16, 18 
Cordotomy, 100-101, 222 
Corticosteroids 

advantages and disadvantages of, 44 

depression and, 131 

description of, 65 

dosing data for, 66 

for spinal cord compression pain, 31 
Counterstimulation 

description of, 79-80 

explanation of, 185 

scientific evidence for, 223, 224 
Cryotherapy, 185. See Cutaneous 

stimulation 
Cutaneous stimulation 

advantages and disadvantages of, 45 

description of, 76-78 

recommendations regarding, 75, 76 

scientific evidence for, 223 

used for children, 126 



D 

Deafferentiation pain, 186 
Delirium 

effect on pain treatment of, 134 

in elderly patients, 129, 134 

prevalence of, 130 

as side effect of drugs, 131, 134 
Dementia 

delirium vs., 134 

in elderly patients, 129 
Demerol. See Meperidine 
Dependence. See Physical dependence 
Depression. See also Antidepressants 

in HIV patients, 140 

management of, 131 

prevalence of, 9, 130 

risk factors for, 131, 132 

suicide risk due to, 132, 133 
Dexamethasone, 65, 66 
Dextroamphetamine 

dosing data for, 66, 124 

use of, 61 

used for children, 124 
Dezocine, 50 
Diazepam, 111 
Didanosine, 140 
Diflunisal (Dolobid), 48 
Dilaudid. See Hydromorphone 
Diphenhydramine, 65 
Distraction 

advantages and disadvantages of, 44 

description of, 82, 186 

scientific evidence for, 223, 224 

use of, 28 

used for children, 126 
Dolobid (diflunisal), 48 
Dolophine. See Methadone 
Dorsal rhizotomy, 100, 222 
Doxepin, 66 

Drug therapy. See also Adjuvant 
analgesics; Analgesics; 
NSAIDs; Opioids; Pain 
management; specific drugs 

administration methods for, 39-41, 
45, 55-60, 222, 224 

discharge planning and, 71 

influence of concurrent medical 
conditions on, 70-71 

Medicare reimbursement policies 
regarding inpatient vs. 
outpatient, 19 

not recommended for cancer pain 
treatment, 71-73 



249 



Management of Cancer Pain 



overview of, 3-4, 40-41 
pain assessment following, 28 
patient-controlled, 59-60, 123 
patient education regarding, 84 
for procedural pain, 108, 110-112 
recommendations regarding, 39-40 
scientific evidence for, 222, 224 
to treat cancer, 70 
WHO approach to, 12, 14, 41, 45 
Dysesthesis, 186 

E 

Education. See Family education; 
Patient education 

Eland Color Scale, 234-235 

Elderly patients 

drug monitoring in, 47, 111 
drug side effects in, 129-130, 134 
pain assessment for, 115, 129 
pain management in, 129-130 
patient-controlled analgesia used 

by, 130 
prevalence of pain in, 127-129 
recommendations regarding, 115 
rectal opioids in, 56 
renal dysfunction in, 47, 71 

Emulsion of local anesthetics 
(EMLA), 111,224 

Endorphins, 102 

Epidural 

explanation of, 186 
opioid administration through, 
62,126 

Epidural metastases, 30-31 

Equianalgesic, 186 

Ethanol, 96 

Etidronate, 69 

Etodolac (Lodine), 48 

Exercises 

description of, 78-79 
recommendations regarding, 75, 76 
for relaxation, 242-245 
scientific evidence for, 223 

F 

Families 

of children with HIV, 140-141 
pain reduction due to presence 

of, 126, 224 
role in pain assessment and control, 

10-11 
substance abuse within, 141 
Family education 

regarding pain and pain 

management, 16 



sources of printed information for, 85 
Fenoprofen calcium (Naif on), 48 
Fentanyl 

advantages and disadvantages of, 42 

description of, 49-50 

intraspinal, 58 

for procedural pain, 111 

transdermal, 42, 51, 53, 56, 111, 122. 
See also Transdermal opioids 

use of, 45, 53 

used for children, 123 

withdrawal symptoms from, 51 
Financial costs, 19-20 
Flowchart for Pain Management 

Documentation, 240 
Food and Drug Administration 
(FDA), 18 



Gustave-Roussy Child Pain Scale, 120 

H 

Hallucinations, 64 

Haloperidol, 63 

Health care professionals, 17, 18 

Health care system, 17 

Herpes zoster infection, 96 

HIV. See Human immunodeficiency 

virus (HIV) 
Home care settings, 29 
Hormonal therapy, 70, 101 
Horner's syndrome, 186 
Human immunodeficiency virus 
(HIV), 1, 5, 116, 139-141 
Hydrocodone 

description of, 49-50 

dosing data for, 52, 54 

use of, 41,45 

withdrawal symptoms from, 51 
Hydromorphone 

administration methods for, 56, 58 

description of, 49-50 

dosing data for, 52, 54 

use of, 45, 53 

used for children, 123 

withdrawal symptoms from, 51 
Hydroxyzine 

advantages and disadvantages of, 44 

to control nausea and vomiting, 63 

description of, 68 

dosing data for, 66 
Hypercalcemia 

as complication of bone 
metastases, 30 



250 



Index 



management of, 69 
Hyperpathia, 186 
Hypnosis 

advantages and disadvantages of, 45 

description of, 86, 186 

for procedural pain, 113 

scientific evidence for, 223, 224 
Hypophysectomy, 101, 222 
Hypotension 

opioid antagonists to reverse, 62 

as side effect of methotrimeprazine, 68 

i 

Iatrogenic, 186 
Ibuprofen, 48 
Imagery 

advantages and disadvantages of, 44 

description of, 81-82, 186 

scientific evidence for, 223, 224 

used for children, 126 
Imipramine, 66 
Immobilization 

description of, 79 

recommendations regarding, 75-77 

scientific evidence for, 223 
Implanted pumps, 60. See also 
Intraspinal administration 
Incident pain. See Movement-related 

pain 
Infants. See also Children; Neonates 

analgesics used for, 124-125 

epidural analgesia for, 126 

pain in, 116-117 

recommendations regarding 

assessment and treatment of, 115 

use of pain medication for, 110 
Initial Pain Assessment Tool, 26, 230 
International Association of 
Laryngectomees, 86 
Intramuscular administration, 57, 73 
Intraspinal administration 

advantages and disadvantages of, 
60, 102 

dose range for, 58 

indications for, 57-58 

long-term, 58-59 

used for elderly patients, 130 
Intrathecal, 186 
Intravenous infusion 

advantages and disadvantages of, 
43, 55, 57, 62 

patient-controlled, 59-60 

for procedural pain, 111 

used for children, 122 



Intraventricular infusion, 59, 103 
Invasive therapies. See also 

Neurosurgery; Radiation 
therapy; specific techniques; 
Surgery 
overview of, 90 

recommendations regarding, 89-90 
scientific evidence for, 222-223 
Isocarboxazid, 70 
Isoniazid, 140 

K 

Ketamine, 110 

Ketoprofen (Orudis), 48 

Ketorolac tromethamine (Toradol), 48 

L 

Lancinating, 186 

Legislation, 3, 16, 18-19. See also specific 

legislation; State legislation 
Levo-Dromoran. See Levorphanol 
Levorphanol 

description of, 49-50 

dosing data for, 52, 54, 64 

side effects of, 134 

use of, 45, 71 

withdrawal symptoms from, 51 
Lidocaine 

dosing data for, 66 

used for elderly patients, 129 

used for nerve block, 95 
Lodine (Etodolac), 48 
Lumbar puncture 

in children, 116 

procedural pain from, 113-114 

M 

Magnesium salicylate, 48 
Massage 

description of, 78 

scientific evidence for, 223 
Meclofenamate sodium (Meclomen), 48 
Meclomen (meclofenamate sodium), 48 
Medicare, 19 

Medication. See Drug therapy 
Mefenamic acid (Ponstel), 48 
Memorial Pain Assessment Card, 28, 232 
Meperidine 

cautions for use of, 50, 72, 73, 
110, 131 

dosing data for, 52, 54 

hepatic or renal dysfunction and, 71 

for procedural pain, 111 

side effects of, 134 



251 



Management of Cancer Pain 



use of, 39, 50 

used for children, 123 
Methadone 

description of, 49-50 

dosing data for, 52, 54, 64 

hepatic or renal dysfunction and, 71 

maintenance programs using, 
135-137 

side effects of, 65, 134 

use of, 45, 137 

used for children, 123 

used for elderly patients, 129 

withdrawal symptoms from, 51 
Methohexital, 110 
Methotrimeprazine, 68 
Methylphenidate, 61, 63, 66 

dosing data for, 66, 124 

use of, 61,63 

used for children, 124 
Metoclopramide, 53, 63 
Mexiletine, 66, 67 
Midazolam, 108, 111 
Minority patients, 138-139 
Mixed opioid agonist-antagonists. See 
also Opioids 

cautions for use of, 50 

description of, 49, 50, 186 

recommendations for use of, 39 
Monoamine oxidase inhibitors, 70, 131 
Morphine 

administration methods for, 56, 58 

for conscious sedation, 112 

description of, 49-50 

dosing data for, 51, 52, 54, 125 

intraspinal, 58 

intraventricular, 59 

methotrimeprazine used with, 68 

for procedural pain, 111 

side effects of, 53, 65, 134 

use of, 45, 136-137 

used for infants and children, 
122, 123, 125, 126 

withdrawal symptoms from, 51 
Movement-related pain, 186 
Mucositis 

assessment of, 37, 38 

diagnosis of, 37-38 

drug administration during, 55 

explanation of, 187 
Music therapy, 187 
Myeloma, 33 
Myelotomy, 101, 222 
Myoclonus, 64, 131 
Myofascial pain, 187 



N 

Nalbuphine 

description of, 50 

risks related to, 72 
Naif on (fenoprofen calcium), 48 
Naloxone 

in children, 124 

effects of, 50, 62 

recommendations for use of, 40, 
63,72 

to reverse hypoventilation, 113 
Naltrexone, 72 
Naprosyn (naproxen), 48 
Naproxen (Naprosyn), 48 
Naproxen sodium (Anaprox), 48 
Nasal opioids, 56 

National Cancer Information Service, 87 
National Cancer Institute Workshop 

on Cancer Pain, 8 
National Coalition for Cancer 
Survivorship, 86, 87 
Nausea, 63 
Neonates. See also Children; Infants 

analgesics used for, 124-125 

pain in, 116-117 

use of pain medication for, 110 
Nerve blocks. See also Neurolytic blocks 

for abdominal pain, 37 

complications from, 97, 98 

description of, 95-98, 186 

for postsurgical pain, 35 

purpose of, 95 
Neuopathic pain, 103 
Neuraxial opioid infusion, 102 
Neuritis, 97 

Neuroablation, 100-101 
Neuroaugmentation. See also 

Transcutaneous electrical nerve 
stimulation 

advantages and disadvantages of, 45 

description of, 102 

scientific evidence for, 223 
Neuroleptic agents 

description of, 68 

dosing data for, 66 
Neurologic examination, 25, 27 
Neurolytic blocks. See also Nerve blocks 

advantages and disadvantages of, 43 

celiac, 97 

description of, 97-98, 187 

indications for, 97 

recommendations regarding, 89, 98 

scientific evidence for, 223 



252 



Index 



Neuropathic pain 

diagnosis of, 33-36 

evaluation for, 26 

explanation of, 187 

management of, 67 
Neurosurgery. See also Surgery 

to implant drug infusion systems, 102 

neuroablation, 100-101 

neuroaugmentation, 102 

for pain relief, 99-100 

scientific evidence for, 222 
Nitrous oxide, 110, 112, 222, 224 
Nociceptive pathways 

explanation of, 187 

functioning of, 11-12 
NSAIDs. See also Acetaminophen; 
specific drugs 

administration methods for, 47 

advantages and disadvantages of, 

42, 46-47 
cost of, 20 

description of, 46-47, 49, 187 
dosing data for, 48, 49 
preparations combining opioids 

with, 52 
scientific evidence for, 222, 224 
use of, 39-41, 49 
used for children, 120-121 
used for elderly patients, 129 
used with opioids and adjuvant 

analgesics, 46, 53 
Numorphan. See Oxymorphone 

o 

Opiate receptors 

explanation of, 187 
NSAIDs and, 46 
Opioid agonists 

description of, 49, 50, 187 
recommendations for use of, 39, 72 
Opioid antagonists, 62, 63, 72 
Opioid partial agonist, 49, 50, 187 
Opioids. See also Drug therapy 
action of endogenous, 12 
adjuvant drugs used with, 53 
administration methods for, 39, 42, 

43, 55-60, 62. See also specific 
methods 

advantages and disadvantages of, 42 
cautions regarding use of, 62 
description of, 49-50 
dosing data for, 51-55, 122-123 
fear regarding use of, 16 
following neurolysis, 89 



full, 49-50 

hypersensitivity to, 62 

legal regulation of, 16, 18-19 

long-term use of, 39 

minority patients and, 138 

mixed agonist-antagonist, 49, 50 

NSAIDs used with, 46, 53 

partial agonist, 49, 50 

for procedural pain, 110-113 

recommendations for use of, 39-41, 45 

renal insufficiency and, 71 

scientific evidence for, 222, 224 

side effects of, 40, 50, 61-65, 124 

substance abuse and, 135-138 

tolerance and physical dependence 

on, 39, 50-51, 136 
used for children, 121-124 
used for elderly patients, 129-130 
used for neonates and infants, 

124-125 
withdrawal symptoms from, 51, 96 

Orudis (ketoprofen), 48 

Oucher, 118 

Outpatients 

pain assessment for, 29 
substance abuse by, 137 

Oxycodone 

description of, 49-50 
dosing data for, 52, 54 
used for children, 123 

Oxymorphone, 52, 56 

P 

Pain 

as cancer patient problem, iii, v, 1 

discussion of, 7-8, 11-12 

explanation of, 187 

movement-related, 186 

perception of, 12, 128 

procedure-related, 107-114 

quality of life issues related to, 
10-11. See also Quality of life 

social spiritual, and physical effects 
of, 11 
Pain Affect Faces Scale, 238 
Pain assessment 

for children, 117 

of common cancer pain syndromes, 
3, 29-38. See also specific 
syndromes 

for elderly patients, 129 

initial, 23-28 

of new pain, 38 

ongoing, 28-29 



253 



Management of Cancer Pain 



recommendations regarding, 23, 
115, 129 

role of family in, 10-11 

role of patients in, 3 
Pain assessment instruments 

for adults, 24, 26-27, 129, 228-232 

for children, 118-120, 233-238 

for elderly patients, 129 

for non-English speaking patients, 29 

use of, 24, 26-27 
Pain distress scales, 28, 231 
Pain Experience History, 233 
Pain intensity scales 

application of, 26-27 

discrepancies in use of, 28 
Pain management. See also 

Drug therapy; Invasive therapies 

advantages and disadvantages of 
various forms of, 42-45 

barriers to, 3, 16-19 

in children. See Children 

in cognitively impaired patients, 129 

cost and reimbursement for, 19-20 

documentation of, 145, 239, 240 

in elderly. See Elderly patients 

flowchart for continuing, 12, 13 

in minority patients, 138-139 

monitoring quality of, 143-146 

in neonates and infants, 110, 
115-117, 124-126. See also 
Children 

nonpharmacologic, 4 

overview of, 12-16 

in patients with AIDS, 1, 116, 134, 
139-141 

pharmacologic, 3-4 

priority associated with, 8 

for procedural pain, 108-114 

role of family in, 10-11 

in substance abusing patients, 4-5, 
134-138 
Pain Management Log, 239 
Pain management plans 

illustration of, 74 

recommendations for use of, 40 

requirements for, 71-72 
Pain management strategies 

assessment in children of, 127, 128 

cost involved in various, 20 

hierarchy of, 14, 15 
Pain syndromes. See also specific pain 
syndromes 

assessment of, 3, 29-38 

description of common, 29-38 



postsurgical, 35, 105 

professional awareness of, 23 
Palliative therapies. See also 

Chemotherapy; Radiation 
therapy; Surgery 

explanation of, 187 

radiation, 89-94 

recommendations regarding, 89 
Pamidronate, 69 
Pancoast tumor, 187 
Panel recommendations 

on curricula for health 
professionals, 3 

on invasive therapies, 89-90 

on legislation and regulatory 
policies on use of opioids, 19 

overview of, 7 

on pain assessment, 23 

on pain in special populations, 115-116 

on pain management monitoring, 143 

on pharmacologic management, 39-40 

on physical modalities, 75 

on procedural pain, 107 
Parents. See Families 
Pastoral counseling, 45, 75 
Patient-controlled analgesia (PCA) 

description of, 59-60, 187 

recommendations regarding, 62 

substance abuse and, 136-137 

used by children, 123 

used by elderly patients, 130 
Patient education 

advantages and disadvantages of, 45 

goals and benefits of, 83-84 

regarding pain and pain 
management, 16 

scientific evidence for, 223 

sources of printed information for, 85 
Patients. See also Children; Infants 

drug therapy and concurrent 
medical conditions in, 70-71 

extent of pain in, 7-8 

financial resources of, 19-20 

lose of control in, 10 

minority, 138-139 

in outpatient settings, 29, 137 

pain assessment in non-English- 
speaking, 29 

pain management plans for 
discharged, 40, 71-73 

pain management problems for, 17 

as primary pain assessment source, 
3, 24 

substance-abusing, 4-5, 115, 134-138 



254 



Index 



Peer support groups 

advantages and disadvantages of, 45 

description of, 86-87 

methods to locate, 87 

recommendations regarding, 75 
Pentazocine 

description of, 50 

hepatic or renal dysfunction and, 71 

risks related to, 72 
Pentobarbital, 108 

Percutaneous temporary catheter. See 
also Intraspinal administration 

use of, 60, 98-99 

used for children, 122 
Peripheral neurectomy, 100, 222 
Permanent silicone-rubber epidural, 60. 
See also Intraspinal 
administration 
Pharmacologic management. See 

Drug therapy 
Phenol, 96 
Phenothiazines 

to counteract side effects of 
opioids, 53 

description of, 68 
Phenylzine sulfate, 70 
Phenytoin 

description of, 65, 140 

dosing data for, 66 

drug interactions and, 70 

monitoring of patients receiving, 67 
Phosphorus-32-orthophosphate, 93 
Physical dependence. See also Substance 
abusing patients 

explanation of, 188 

on opioids, 50-51, 135 
Physical examination, 25, 27 
Physical modalities 

explanation of, 76, 188 

forms of, 76-80 

recommendations regarding, 75 

scientific evidence for, 223 
Physical therapy, 126 
Pituitary, chemical ablation of, 98 
Placebos 

knowledge regarding, 12 

recommendations for use of, 40, 69 

response from, 69 
Plexopathies 

description of, 93-94 

diagnosis of, 31-33 
Poker Chip Tool Instrument Sheet, 

118,238 
Ponstel (mefenamic acid), 48 



Positioning, 78-79, 126 
Postherpetic neuralgia, 33-36, 96 
Postsurgical pain syndromes, 35 
Prednisone, 65, 66 
Procarbazine, 131-132 
Prochlorperazine, 63 
Progressive muscle relaxation, 188 
Promethazine, 73, 110 
Propofol, 110 
Propoxyphene, 71 
Pruritus, 64, 65 
Pseudoaddiction, 135, 188 
Psychosocial assessment, 25, 27 
Psychosocial interventions 

description of, 80-81, 188 

forms of, 81-87 

recommendations regarding, 75, 81 

scientific evidence for, 223, 224 
Psychostimulants, 66, 224 
Psychotherapy 

advantages and disadvantages of, 45 

description of, 86 

scientific evidence for, 223 
Pyrophosphates, 69 



Quality of life, 2, 10-11 

R 

Radiation therapy 

advantages and disadvantages of, 44 

for bone metastases, 92-93 

cryotherapy following, 77 

indications for palliative, 89 

mucositis in patients receiving, 37-38 

as palliative treatment, 90-91, 94 

for plexopathy, 93-94 

recommendations regarding, 89-91 

scientific evidence for, 223 
Radiopharmaceuticals 

for bone metastases, 89, 93 

scientific evidence for, 223 
Reach to Recovery, 86 
Rectal opioids. See also Opioids 

advantages and disadvantages of, 42 

use of, 55-56, 62 
Reframing 

advantages and disadvantages of, 44 

description of, 82 

scientific evidence for, 223 
Regulatory policies, 3, 16, 18-19 
Reimbursement policies, 19-20 
Relaxation 

advantages and disadvantages of, 44 



255 



Management of Cancer Pain 



description of, 81-82, 188 

exercises for, 242-245 

scientific evidence for, 223, 224 

use of, 28 
Renal dysfunction, 47, 71 
Respiratory depression 

caused by sedation, 113 

in children, 124 

drug therapy for reversal of 
opioid-induced, 40, 62-64 

effect of, 3-4 

in elderly patients, 129 

management of, 63-64 

in neonates and infants, 125 

opioid plus benzodiazepine 
therapy causing, 111 
Rhenium-186, 93 
Rhizotomy, 100, 222 
Rifampin, 70 
Rimadyl (carprofen), 48 

s 

Salsalate 

use of, 46, 47 

used for children, 121 
Samarium-153 phosphonate chelates, 93 
Scientific evidence 

for pain reduction in adults, 
222-223, 225 

for pain reduction in children, 
224-225 
Scopolamine, 63 
Sedation 

conscious, 107, 112-113, 185 

deep, 113 

in elderly patients, 129 

management of, 61, 63 

in neonates and infants, 125 

for procedural pain, 107, 108, 
110-113 

subacute overdose leading to, 64 
Seizures, 64 

Self-reports. See also Pain assessment 
instruments 

for adults, 24, 26-27, 228-232, 239-240 

for children, 118-119, 233-238 
Self-statement, 188 
Sexual function, 64 
Sleep disturbances, 64, 68 
Sodium salicylate 

dosing data for, 48 

use of, 46-47 
Spinal cord compression 

diagnosis of, 30-31 



evaluation for, 26, 29 

management of, 65, 92 
Spinal tractotomy, 100-101 
State legislation, 18. See also Legislation 
Strontium-89, 93 
Structured support 

advantages and disadvantages of, 45 

scientific evidence for, 223 
Subcutaneous implanted injection port, 
60. See also 

Intraspinal administration 
Subcutaneous infusion 

advantages and disadvantages of, 
42, 55, 57, 62 

patient-controlled, 59-60 
Subcutaneous reservoir, 60. See also 

Intraspinal administration 
Substance abusing patients 

distinctions among, 135-136 

overview of, 134-135 

pain management in, 4-5, 136-138 

recommendations regarding, 115, 
136, 138 
Sufentanil, intraspinal, 58 
Suffering, 9-10, 188 
Suicide, 132-133, 140 
Surgery. See also Neurosurgery 

ablative, 43, 99-101, 185 

drug pharmacokinetics following, 
70-71 

pain as consequence of, 105, 222 

pain syndromes following, 35 

principles of, 103 

scientific evidence for, 222 

T 

Taxol, 34 

Teletherapy, 89 

TENS, 188 

Thermotherapy. See Cutaneous 

stimulation 
Thiopental, 110 
Thought stopping, 113 
Tocainide, 66, 67 
Tolerance 

explanation of, 188 

for opioids, 50-51, 61, 135, 136 
Toradol (ketorolac tromethamine), 48 
Transcutaneous electrical nerve 

stimulation (TENS). See also 
Neuroaugmentation 

advantages and disadvantages of, 45 

description of, 79 

recommendations regarding, 76, 80 



256 



scientific evidence for, 223, 224 

used for children, 126 
Transdermal opioids. See also Opioids 

advantages and disadvantages of, 42 

for procedural pain, 111 

use of, 51, 53, 56, 62 

used for children, 122 
Trazodone, 66 
Trilisate. See Choline magnesium 

trisalicylate 
Tylenol with codeine, 52-55 

u 

Uniform Controlled Substances Act 

(1990 revision), 18-19 
United Ostomy Association, 86 
Urinary retention, 65 



V 

Valproate, 65, 67 

Varicella-zoster virus infection, 36 
Venipunctures, 116 
Vincristine, 34, 140 
Vomiting, 63 

w 

Withdrawal symptoms, 51, 96 
Word-Graphic Rating Scale, 237 
World Health Organization (WHO) 

analgesic ladder of, 12, 14, 41, 45, 120 
on cancer pain management, 8, 138 
views on use of opioids, 18 

z 

Zalcitabine, 140 



i* U.S. GOVERNMENT PRINTING OFFICE: 1995-386-981/33643 



257 



Availability of Guidelines 

For each Clinical Practice Guideline developed under the sponsor- 
ship of the Agency for Health Care Policy and Research (AHCPR), 
several versions are produced to meet different information needs. 

The Guideline Report contains background information, method- 
ology, scientific evidence tables, and a comprehensive bibliography. 

The Clinical Practice Guideline and the Quick Reference Guide 
for Clinicians (for this guideline, pediatric and adult versions), are 
companion documents for use as desk-top references for clinical 
decisionmaking in day-to-day care of patients. Recommendations, 
algorithms or flow charts, tables and figures, and pertinent references 
are included. 

A Patient's Guide, available in English and Spanish, and for this 
guideline, pediatric and adult versions, is an informational booklet for 
the general public to increase consumer knowledge and involvement 
in health care decisionmaking. 

Guideline information also will be available for on-line retrieval 
through the National Library of Medicine, the National Technical 
Information Service, and some computer-based information 
systems of professional associations, nonprofit organizations, and 
commercial enterprises. 

To order cancer pain guideline products or to obtain further 
information on their availability, call the National Cancer Institute 
toll-free at 1-800-4-CANCER or write to the AHCPR Clearinghouse, 
Cancer Pain Guideline, P.O. Box 8547, Silver Spring, MD 20907. 



Single copies of this publication are available for sale from the Government Printing 
Office; stock no. 017-022-01 182-4. A 25-percent discount is given for bulk orders of 
100 copies or more. For ordering information or credit card (Visa and Mastercard) 
orders, call (202) 512-1800, or write Superintendent of Documents, P.O. Box 371954, 
Pittsburgh, PA 15205-7954. 



U.S. Department of Health and Human Services 

Agency for Health Care Policy and Research 
Executive Office Center, Suite 501 
2101 East Jefferson Street 
Rockville, MD 20852 

AHCPR Publication No. 94-0592 
March 1994